CHAPTER 16: THE ENDOCRINE SYSTEM

Autocrines

- Are short-distance chemical signals that exert their effects on the same cells that secrete them

The study of hormones and the endocrine organs is called

- Endocrinology - Compared with other organs, the endocrine system's organs are small and unimpressive, but their influence is powerful. - Unlike most organ systems, the endocrine organs are not grouped together but are widely scattered about the body

The hypothalamus controls release of ______ from the _____ gland

- Hormones; Pituitary

Cushing's Disease

- Hypercortisolism caused by an anterior pituitary tumor - Exhibit increased levels of ACTH and cortisol

Antagonsim

- Occurs when one hormone opposes the action of another. For example, insulin, which lowers blood glucose levels, is antagonized by glucagon, which raises blood glucose levels

Parathyroid Glands

- Primary regulators of blood calcium levels - The parathyroid cells secrete parathyroid hormone

Exocrine Glands

- Produce nonhormonal substances, such as sweat and saliva, and have ducts that carry these substances to a membrane surface.

Glucocorticoids

- The glucocorticoids influence the energy metabolism of most body cells and help us resist stressors. - Under normal circumstances, they help the body adapt to intermittent food intake by keeping blood glucose levels fairly constant, and help maintain blood pressure - Glucocorticoid hormones include cortisol (hydrocortisone), cortisone, and corticosterone, but only cortisol is secreted in significant amounts in humans

Interaction of Hormones at Target Cells

- There are 3 types of hormone interactions: permissiveness, synergism, and antagonism

Endocrine Gland Stimuli

- Three types of stimuli trigger endocrine glands to manufacture and release their hormones: humoral, neural, and hormonal stimuli. Some endocrine organs respond to more than one type of stimulus

Intracellular Receptors and Direct Gene Activation

- Unlike water-soluble hormones, the lipid-soluble steroid hormones and thyroid hormone are able to diffuse through the plasma membrane into their target cells - There, they bind to and activate intracellular receptors - The activated receptor-hormone complex then makes its way to the nuclear chromatin and binds to a specific region of DNA - When the receptor-hormone complex binds to DNA, it "turns on" a gene; that is, it prompts transcription of DNA to produce a messenger RNA (mRNA). - The mRNA is then translated on the cytoplasmic ribosomes, producing specific proteins. - These proteins include enzymes that promote the metabolic activities induced by that particular hormone and, in some cases, promote synthesis of either structural proteins or proteins to be exported from the target cell

Type 1 and Type 2 Diabetes Mellitus

- When the pancreas does not produce enough insulin, type 1 diabetes mellitus results - When the pancreas produces sufficient insulin, but the body fails to respond to it, type 2 diabetes mellitus results - In both cases, glucose remains in the blood and the body's cells are unable to take it up to serve as the primary fuel for metabolism

Plasma Membrane Receptors and Second Messenger Systems

- With the exception of thyroid hormone, amino acid-based hormones exert their signaling effects through intracellular second messengers generated when a hormone binds to a receptor in the plasma membrane. - Cyclic AMP (cAMP), which is used by neurotransmitters and olfactory receptors

A hormone produces one or more of the following changes

1. Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels 2. Stimulates synthesis of enzymes and other proteins within the cell 3. Activates or deactivates enzymes 4. Induces secretory activity 5. Stimulates mitosis

What are the 2 major lobes of the pituitary gland?

1. The posterior pituitary (lobe) is composed largely of neural tissue such as pituicytes (glia-like supporting cells) and nerve fibers - It releases neurohormones (hormones secreted by neurons) received ready-made from the hypothalamus. - Consequently, this lobe is a hormone-storage area and not a true endocrine gland that manufactures hormones - The posterior lobe plus the infundibulum make up the region called the neurohypophysis 2. The anterior pituitary (lobe), or adenohypophysis is composed of glandular tissue (adeno = gland). - Known as the master endocrine gland - It manufactures and releases a number of hormones - Hypophyseal branches of the internal carotid arteries deliver arterial blood to the pituitary. The veins leaving the pituitary drain into the dural sinuses

The large, lipid-laden cortical cells are arranged in three layers or zones, what are they?

1. Zona glomerulosa The cell clusters forming this superficial layer produce mineralocorticoids, hormones (such as aldosterone) that help control the balance of minerals and water in the blood 2. Zona fasciculata The cells of this middle layer, arranged in more or less linear cords, mainly produce the metabolic hormones called glucocorticoids (such as cortisol). 3. Zona reticularis The cells of this innermost layer, next to the adrenal medulla, have a netlike arrangement. They mainly produce small amounts of adrenal sex hormones, or gonadocorticoids

The concentration of a circulating hormone in blood at any time reflects what?

- (1) its rate of release and (2) the speed at which it is inactivated and removed from the body - However, most hormones are removed from the blood by the kidneys or liver, and the body excretes their breakdown products in urine or, to a lesser extent, in feces - As a result, the length of time for a hormone's blood level to decrease by half, referred to as its half-life, varies from a fraction of a minute to a week. - Water-soluble hormones have the shortest half-lives because they are rapidly removed from the blood by the kidneys

What determines how a hormone functions?

- A hormone's chemical structure determines one of its critical properties: its solubility in water - Its water solubility in turn affects how that hormone is transported in the blood (which is mostly water), how long it lasts before it is degraded, and what receptors it can act upon - Although a large variety of hormones are produced, nearly all of them can be classified chemically either as based on amino acids or as steroids

Atrial Natriuretic Peptide (ANP)

- A hormone, secreted by the heart, that normally reduces blood pressure, inhibits drinking, and promotes the excretion of water and salt at the kidneys - Inhibits the renin-angiotensin-aldosterone mechanism - Blocks renin and aldosterone secretion

Oxytocin

- A strong stimulant of uterine contraction, oxytocin is released in significantly higher amounts during childbirth and in nursing women Contractions During Birth - The number of oxytocin receptors in the uterus peaks near the end of pregnancy, and uterine smooth muscle becomes more and more sensitive to the hormone's stimulatory effects. - Stretching of the cervix of the uterus as birth nears dispatches afferent impulses to the hypothalamus. - The hypothalamus responds by synthesizing oxytocin and triggering its release from the posterior pituitary - Oxytocin acts via the PIP2−Ca2+ second-messenger system to mobilize Ca2+, allowing stronger contractions. - As blood levels of oxytocin rise, the expulsive contractions of labor gain momentum and finally end in birth Lactation - Oxytocin also acts as the hormonal trigger for milk ejection (the "letdown" reflex) in women whose breasts are producing milk in response to prolactin - Both natural and synthetic oxytocic drugs are used to induce labor or to hasten labor that is progressing slowly. Less frequently, oxytocic drugs are used to stop postpartum bleeding - Oxytocin also acts as a neurotransmitter in the brain. There, it is involved in sexual and affectionate behavior (as the "cuddle hormone"), and promotes nurturing, couple bonding, and trust

Adrenocorticotropic Hormone (ACTH)

- ACTH or corticotropin, is secreted by the corticotropic cells of the anterior pituitary - ACTH stimulates the adrenal cortex to release corticosteroid hormones, most importantly glucocorticoids that help the body resist stressors - ACTH release, elicited by hypothalamic corticotropin-releasing hormone (CRH), has a daily rhythm, with levels peaking in the morning, shortly before awakening. - Rising levels of glucocorticoids feed back and block secretion of CRH and ACTH release. - Internal and external factors that alter the normal ACTH rhythm by triggering CRH release include fever, hypoglycemia (low blood glucose levels), and stressors of all types

Hypothyroidism

- AKA myxedema - Symptoms: low metabolic rate, feeling chilled, constipation, thick dry skin and puffy skin, edema - A goiter occurs when hypothyroidism is caused by (1) primary failure of the thyroid gland or (2) an iodine-deficient diet that prevents the thyroid gland from producing TH - The low levels of TH remove inhibition for secretion of TSH, and its levels rise - When hypothyroidism is secondary to hypothalamic or anterior pituitary failure, TRH and/or TSH levels fall and no goiter is produced

Direct Actions on Metabolism

- Acting directly, GH exerts metabolic effects. It mobilizes fats from fat depots for transport to cells, increasing blood levels of fatty acids and encouraging their use for fuel. - It also decreases the rate of glucose uptake and metabolism, conserving glucose. - In the liver, it encourages glycogen breakdown and release of glucose to the blood - This glucose sparing action, which raises blood glucose levels, is called the anti-insulin effect of GH because its effects oppose those of insulin. - In addition, GH increases amino acid uptake into cells and their incorporation into proteins

Adipose Tissue

- Adipose cells release leptin, which serves to tell your body how much stored energy (as fat) you have - The more fat you have, the more leptin there will be in your blood - Leptin binds to CNS neurons concerned with appetite control, producing a sensation of satiety. It also appears to stimulate increased energy expenditure - Two other hormones released by adipose cells affect the sensitivity of cells to insulin. - Resistin is an insulin antagonist, while adiponectin enhances sensitivity to insulin

ACTH

- Adrenocorticotropic hormone - Under normal circumstances, ACTH released by the anterior pituitary has little or no effect on aldosterone release. - However, when a person is severely stressed, the hypothalamus secretes more corticotropin-releasing hormone (CRH), and the resulting rise in ACTH blood levels steps up the rate of aldosterone secretion to a small extent. - The resulting increase in blood volume and blood pressure helps deliver nutrients and respiratory gases during the stressful period

Target Cells

- All major hormones circulate to virtually all tissues, but a hormone influences the activity of only those tissue cells that have receptors for it. These cells are its target cells - Hormones bring about their characteristic effects by altering target cell activity, increasing or decreasing the rates of normal cellular processes - The precise response depends on the target cell type. - For example, when the hormone epinephrine binds to certain smooth muscle cells in blood vessel walls, it stimulates them to contract

Endocrine Glands

- Also called ductless glands, produce hormones and lack ducts. - They release their hormones into the surrounding tissue fluid (endo = within; crine = to secrete), and typically have a rich vascular and lymphatic drainage that receives their hormones - Most of the hormone-producing cells in endocrine glands are arranged in cords and branching networks, which maximizes contact between them and the surrounding capillaries - The endocrine glands include the pituitary, thyroid, parathyroid, adrenal, and pineal glands - The hypothalamus, along with its neural functions, also produces and releases hormones, so we consider the hypothalamus a neuroendocrine organ. - In addition, several organs, such as the pancreas, gonads (ovaries and testes), and placenta, contain endocrine tissue

Goiter

- An enlargement of the thyroid gland - Both hypothyroidism and hyperthyroidism can result in the production of a goiter - A goiter is the result of excessive stimulation of the thyroid gland

Paracrines

- Are also short-distance chemical signals. They act locally (within the same tissue) but affect cell types other than those releasing the paracrine chemicals

The Pancreas

- Behind the stomach in the abdomen---> mixed gland composed of both endocrine and exocrine glands - Produce digestive enzymes as well as insulin and glucagon - Acinar cells, forming the bulk of the gland, produce an enzyme-rich juice that is carried by ducts to the small intestine during digestion - Scattered among the acinar cells are approximately a million pancreatic islets (also called islets of Langerhans), tiny cell clusters that produce pancreatic hormones - The islets contain two major populations of hormone-producing cells: 1. Alpha Cells: release glucagon and are fewer in number 2. Beta Cells: release insulin and are more numerous - These cells act as tiny fuel sensors, secreting glucagon and insulin appropriately during the fasting and fed states - Their effects are antagonistic: Glucagon is a hyperglycemic hormone (increases blood glucose), whereas insulin is a hypoglycemic hormone (decreases blood glucose)

Metabolism

- Broad range of biochemical reactions occurring in the body - Includes anabolism and catabolism - Anabolism: the building up of small molecules into larger, more complex molecules via enzymatic reactions - Catabolism: breakdown of large, complex molecules into smaller molecules via enzymatic reactions - The breaking of chemical bonds in catabolism releases energy that the cell can use to perform activities such as forming ATP - The cell does not use all of the energy---> released as heat to maintain body temp

Calcitonin

- Calcitonin a polypeptide hormone released by the parafollicular, or C, cells of the thyroid gland in response to a rise in blood Ca2+ levels, does not have a known physiological role in humans

Hormone Receptors

- Cells respond to a hormone if they have a receptor for that hormone - In order for a target cell to respond to a hormone, the cell must have specific receptor proteins on its plasma membrane or in its interior to which that hormone can bind - A hormone receptor responds to hormone binding by prompting the cell to perform, or turn on, some gene-determined "preprogrammed" function - Although binding of a hormone to a receptor is required, the degree of target cell activation depends equally on three other factors: 1. Blood levels of the hormone 2. Relative numbers of receptors for that hormone on or in the target cells 3. Affinity (strength) of the binding between the hormone and the receptor - The first two factors change rapidly in response to various stimuli and changes within the body. - As a rule, for a given level of hormone in the blood, having a large number of high-affinity receptors produces a pronounced hormonal effect, and having a smaller number of low-affinity receptors reduces the target cell response or causes outright endocrine dysfunction

The PIP2- Calcium Signaling Mechanism

- Certain hormones use second messengers other than cAMP. For example, in the PIP2-calcium signaling mechanism, intracellular calcium ions act as a second messenger - The PIP2-calcium signaling mechanism involves a G protein (Gq) and a membrane-bound effector, in this case an enzyme called phospholipase C - Phospholipase C splits a plasma membrane phospholipid called PIP2 (phosphatidyl inositol bisphosphate) into two second messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3). - DAG, like cAMP, activates a protein kinase enzyme, which triggers responses within the target cell. In addition, IP3 releases Ca2+ from intracellular storage sites. - The liberated Ca2+ also takes on a second-messenger role, either by directly altering the activity of specific enzymes and channels or by binding to the intracellular regulatory protein calmodulin. - Once Ca2+ binds to calmodulin, it activates enzymes that amplify the cellular response

Heart

- Chambers of the heart called atria contain specialized cardiac muscle cells that secrete atrial natriuretic peptide (ANP). - ANP decreases the amount of sodium in the extracellular fluid, thereby reducing blood volume and blood pressure

What determines the effect that cAMP has in a given cell?

- Cyclic AMP is a very common second messenger that has many different effects in many different cells - This is determined by the specific protein kinases that cell contains, and the substrates within that cell available for phosphorylation - Since some G proteins inhibit rather than activate adenylate cyclase, thereby reducing the cytoplasmic concentration of cAMP, even slight changes in levels of hormones that have opposite effects on cAMP levels can influence a target cell's activity

Hypocortisolism or Addison's Disease

- Decreased cortisol in the blood - Can occur b/c of adrenal insufficiency - Lower cortisol is caused by adrenal cortex destruction and ACTH levels are elevated as a compensatory effect - Secondary adrenal insufficiency also results in low levels of cortisol, usually caused by damage to the anterior pituitary which reflect low ACTH levels

Antidiuretic Hormone (ADH)

- Diuresis is urine production, so an antidiuretic is a substance that inhibits or prevents urine formation. - Antidiuretic hormone (ADH) prevents wide swings in water balance, helping the body avoid dehydration and water overload - Hypothalamic neurons called osmoreceptors continually monitor the solute concentration (and thus the water concentration) of the blood. - When solutes threaten to become too concentrated (as might follow excessive perspiration or inadequate fluid intake), the osmoreceptors transmit excitatory impulses to the hypothalamic neurons, which release ADH. - ADH targets the kidney tubule cells, which respond by reabsorbing more water from the forming urine and returning it to the bloodstream - As a result, less urine is produced and the solute concentration of the blood declines. As solute levels fall, the osmoreceptors stop depolarizing, effectively ending ADH release. - Other stimuli triggering ADH release include pain, low blood pressure, and such drugs as nicotine, morphine, and barbiturates - Drinking alcoholic beverages inhibits ADH secretion and causes copious urine output. The dry mouth and intense thirst of a "hangover" reflect this dehydrating effect. Drinking lots of water also inhibits ADH release - Under certain conditions, such as severe blood loss, exceptionally large amounts of ADH are released, causing vasoconstriction and raising blood pressure. This response targets different ADH receptors found on vascular smooth muscle. For this reason, ADH is also called vasopressin

Gastrointestinal Tract

- Enteroendocrine cells are hormone-secreting cells sprinkled in the mucosa of the gastrointestinal tract - These scattered cells release several peptide hormones that help regulate a wide variety of digestive functions - Enteroendocrine cells also release amines such as serotonin, which act as paracrines, diffusing to and influencing nearby target cells without first entering the bloodstream. - Enteroendocrine cells have been referred to as paraneurons because they are similar in certain ways to neurons and many of their hormones and paracrines are chemically identical to neurotransmitters.

What are the 2 kinds of glands in the body?

- Exocrine and Endocrine Glands (refer to ch. 4)

Plasma Concentration of Potassium

- Fluctuating blood levels of K+ directly influence the zona glomerulosa cells in the adrenal cortex. Increased K+ stimulates aldosterone release, whereas decreased K+ inhibits it.

Gonadotropins (FSH and LH)

- Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are referred to collectively as gonadotropins. They regulate the function of the gonads (ovaries and testes) - In both sexes, FSH stimulates production of gametes (sperm or eggs-stimulates ovarian follicle maturation) and LH promotes production of gonadal hormones (estrogen, progesterone, and testosterone) - In females, LH works with FSH to cause an egg-containing ovarian follicle to mature. LH then triggers ovulation and promotes synthesis and release of ovarian hormones (estrogen and progesterone) - In males, LH stimulates the interstitial cells of the testes to produce the male hormone testosterone - During puberty, the gonadotropic cells of the anterior pituitary are activated and gonadotropin levels rise, causing the gonads to mature. - In both sexes, gonadotropin-releasing hormone (GnRH) produced by the hypothalamus prompts gonadotropin release. - Gonadal hormones, produced in response to the gonadotropins, feed back to suppress FSH and LH release

Indirect Actions on Growth

- GH mediates most of its growth-enhancing effects indirectly via a family of growth-promoting proteins called insulin-like growth factors (IGFs) - The liver, skeletal muscle, bone, and other tissues produce IGFs in response to GH. IGFs produced by the liver act as hormones, while IGFs made in other tissues act locally within those tissues (as paracrines) - IGFs stimulate actions required for growth: 1. Uptake of nutrients from the blood and their incorporation into proteins and DNA, allowing growth by cell division 2. Formation of collagen and deposition of bone matrix - Although GH stimulates most body cells to enlarge and divide, its major targets are bone and skeletal muscle. - Stimulation of the epiphyseal plate leads to long bone growth, and stimulation of skeletal muscles increases muscle mass.

Glucagon

- Glucagon is a potent hyperglycemic agent - The major target of glucagon is the liver, where it promotes the following actions: 1. Breakdown of glycogen to glucose (glycogenolysis) 2. Synthesis of glucose from lactic acid and from noncarbohydrate molecules (gluconeogenesis) 3. Release of glucose to the blood by liver cells, causing blood glucose levels to rise - Humoral stimuli, mainly falling blood glucose levels, prompt the alpha cells to secrete glucagon. - However, sympathetic nervous system stimulation and rising amino acid levels (as might follow a protein-rich meal) are also stimulatory. - Glucagon release is suppressed by rising blood glucose levels, insulin, and somatostatin.

Half-Life, Onset, and Duration of Hormone Activity

- Hormones are potent chemicals, and they exert profound effects on their target organs even at very low concentrations. - Hormones circulate in the blood in two forms—free, or bound to a protein carrier. - In general, lipid-soluble hormones (steroids and thyroid hormone) are not water soluble. - As a result, they must travel in blood attached to proteins of the blood plasma (plasma proteins). - Most others circulate without carriers

Hormones

- Hormones ultimately target most cells of the body, producing widespread and diverse effects. - The major processes that these "mighty molecules" control and integrate include: 1. Reproduction 2. Growth & Development 3. Maintenance of electrolyte, water, and nutrient balance of the blood 4. Regulation of cellular metabolism and energy balance 5. Mobilization of body defenses - Are long-distance chemical signals that travel in blood or lymph throughout the body

Neural Stimuli

- In a few cases, nerve fibers stimulate hormone release. The classic example of neural stimuli is the response to stress, in which the sympathetic nervous system stimulates the adrenal medulla to release norepinephrine and epinephrine

Hypercortisolism or Cushing's Syndrome

- Increased cortisol in the blood if the increase is caused by an adrenal tumor - Can be iatrogenic (physician induced) when glucocorticoid hormones are induced such as prednisone--> treats arthritis, asthma, or lupus - Also known as "steroid diabetes" because it results in hyperglycemia

Insulin

- Insulin is synthesized as part of a larger polypeptide chain called proinsulin - Insulin's effects are most obvious when we have just eaten. Its main effect is to lower blood glucose levels - But it also promotes protein synthesis and fat storage. - Circulating insulin lowers blood glucose levels in three ways: 1. It enhances membrane transport of glucose (and other simple sugars) into most body cells, especially muscle and fat cells 2. It inhibits the breakdown of glycogen to glucose 3. It inhibits the conversion of amino acids or fats to glucose. - These inhibiting effects counter any metabolic activity that would increase plasma levels of glucose. - Insulin does have important roles in the brain—it participates in neuronal development, feeding behavior, and learning and memory. - After glucose enters a target cell, insulin binding triggers enzymatic activities that: 1. Catalyze the oxidation of glucose for ATP production 2. Join glucose molecules together to form glycogen 3. Convert glucose to fat (particularly in adipose tissue) - As a rule, energy needs are met first, followed by glycogen formation. - Finally, if excess glucose is still available, it is converted to fat. - Insulin also stimulates amino acid uptake and protein synthesis in muscle tissue

Kidneys

- Interstitial cells in the kidneys secrete erythropoietin a glycoprotein hormone that signals the bone marrow to increase production of red blood cells - The kidneys also release renin, which acts as an enzyme to initiate the renin-angiotensin-aldosterone mechanism of aldosterone release

Permissiveness

- Is the situation in which one hormone cannot exert its full effects without another hormone being present. - For example, reproductive system hormones largely regulate the development of the reproductive system, as we might expect - However, thyroid hormone is also necessary (has a permissive effect) for normal timely development of reproductive structures. - Lack of thyroid hormone delays reproductive development

Thymus

- Located deep to the sternum in the thorax is the thymus - Large and conspicuous in infants and children, the thymus shrinks throughout adulthood. By old age, it is composed largely of adipose and fibrous connective tissues - Thymic epithelial cells secrete several different families of peptide hormones, including thymosins, thymulin, and thymopoietins - These hormones are thought to be involved in the normal development of T lymphocytes and the immune response, but their roles are not well understood

Hormonal Stimuli

- Many endocrine glands release their hormones in response to hormones produced by other endocrine organs - For example, releasing and inhibiting hormones produced by the hypothalamus regulate the secretion of most anterior pituitary hormones, and many anterior pituitary hormones in turn stimulate other endocrine organs to release their hormones - As blood levels of the hormones produced by the final target glands increase, they inhibit the release of anterior pituitary hormones and thus their own release - This hypothalamic-pituitary-target endocrine organ feedback loop lies at the very core of endocrinology, and it will come up many times in this chapter. Hormonal stimuli promote rhythmic hormone release, with hormone blood levels rising and falling in a specific pattern

The thyroid gland controls what?

- Metabolism

Transport and Regulation

- Most T4 and T3 released into the blood immediately binds to thyroxine-binding globulins (TBGs) and other transport proteins produced by the liver - Both T4 and T3 bind to target tissue receptors, but T3 binds more tightly and is about 10 times more active. Most peripheral tissues have the enzymes needed to convert T4 to T3 by removing one iodine atom - Falling TH blood levels trigger release of thyroid-stimulating hormone (TSH), and ultimately of more TH. Rising TH levels feed back to inhibit the hypothalamic-anterior pituitary axis, temporarily shutting off the stimulus for TSH release - In infants, exposure to cold stimulates the hypothalamus to secrete thyrotropin-releasing hormone (TRH), which triggers TSH release. - The thyroid gland then releases larger amounts of thyroid hormones, enhancing body metabolism and heat production. - Factors that inhibit TSH release include GHIH, dopamine, and rising levels of glucocorticoids. - Excessively high blood iodide concentrations also inhibit TH release

Gonadocorticoids (Adrenal Sex Hormones)

- Most gonadocorticoids secreted by the adrenal cortex are weak androgens, or male sex hormones, such as androstenedione and dehydroepiandrosterone (DHEA). - Most are converted in tissue cells to more potent male hormones, such as testosterone, and some are converted to estrogens - They contribute to axillary and pubic hair development. - In adult women, adrenal androgens are thought to contribute to the sex drive, and they largely account for the estrogens produced after menopause when ovarian estrogens are no longer produced.

Amino Acid Based

- Most hormones are based on amino acids. - Molecular size varies widely in this group—from simple amino acid derivatives [which include biogenic amines (e.g., epinephrine), and thyroxine], to peptides (short chains of amino acids), to proteins (long polymers of amino acids). - These hormones are usually water soluble and cannot cross the plasma membrane

Prolactin (PRL)

- NOT A TROPIC HORMONE - PRL is a protein hormone structurally similar to GH. Produced by prolactin cells, PRL's only well-documented effect in humans is to stimulate milk production by the breasts - Unlike other anterior pituitary hormones, PRL release is controlled primarily by an inhibitory hormone, prolactin-inhibiting hormone (PIH), now known to be dopamine, which prevents prolactin secretion. Decreased PIH secretion leads to a surge in PRL release - In females, prolactin levels rise and fall in rhythm with estrogen blood levels. - Estrogens stimulate prolactin release, both directly and indirectly. - A brief rise in prolactin levels just before the menstrual period partially accounts for the breast swelling and tenderness some women experience at that time, but because this PRL stimulation is so brief, the breasts do not produce milk. - In pregnant women, PRL blood levels rise dramatically toward the end of pregnancy, and milk production becomes possible. - After birth, the infant's suckling stimulates release of prolactin-releasing factors in the mother, encouraging continued milk production

Growth Hormone (GH)

- NOT A TROPIC HORMONE - Somatotropic cells of the anterior lobe produce growth hormone (GH, also called somatotropin). GH is essentially an anabolic (tissue building) hormone that has both metabolic and growth-promoting actions

Regulation of Secretion

- Negative feedback regulates glucocorticoid secretion. - Cortisol release is promoted by ACTH. - ACTH release is triggered in turn by the hypothalamic releasing hormone CRH. - Rising cortisol levels feed back to act on both the hypothalamus and the anterior pituitary, preventing CRH release and shutting off ACTH and cortisol secretion - Cortisol secretory bursts, driven by patterns of eating and activity, occur in a definite pattern throughout the day and night. - Cortisol blood levels peak shortly before we rise in the morning. The lowest levels occur in the evening just before and shortly after we fall asleep - Various stressors (for example, hemorrhage, infection, or physical or emotional trauma) interrupt the normal cortisol rhythm. - Higher CNS centers override the inhibitory effects of elevated cortisol levels and trigger CRH release. - The resulting increase in ACTH blood levels causes an outpouring of cortisol from the adrenal cortex

Synergism

- Occurs when more than one hormone produces the same effects at the target cell and their combined effects are amplified. - For example, both glucagon and epinephrine cause the liver to release glucose to the blood

Thyroid Hormone

- Often referred to as the body's major metabolic hormone, thyroid hormone (TH) is actually two iodine-containing amine hormones, thyroxine or T4, and triiodothyronine or T3 - Both T4 and T3 are constructed from two linked tyrosine amino acids, but T4 has four bound iodine atoms, and T3 has three - TH affects virtually every cell in the body - It binds to intracellular receptors within the cell's nucleus and initiates transcription of mRNA for protein synthesis. - Effects of thyroid hormone include: 1. Increasing basal metabolic rate and body heat production, by turning on transcription of genes concerned with glucose oxidation. This is the hormone's calorigenic effect (calorigenic = heat producing) 2. Regulating tissue growth and development. TH is critical for normal skeletal and nervous system development and maturation and for reproductive capabilities 3. Maintaining blood pressure by increasing the number of adrenergic receptors in blood vessels

Skeleton

- Osteoblasts in bone secrete osteocalcin, a hormone that prods pancreatic beta cells to divide and secrete more insulin - It also restricts fat storage by adipocytes, and triggers the release of adiponectin. - This improves glucose handling and reduces body fat - Insulin promotes the conversion of inactive osteocalcin to active osteocalcin in bone, forming a two-way conversation between bone and the pancreas

Hormone Secretion by Other Organs

- Other hormone-producing cells occur in various organs including the heart, gastrointestinal tract, kidneys, skin, adipose tissue, skeleton, and thymus

Other Signaling Mechanisms

- Other hormones that bind plasma membrane receptors act on their target cells through different signaling mechanisms. For example, cyclic guanosine monophosphate (cGMP) is a second messenger for selected hormones - Still other hormones, such as insulin and certain growth factors, work without second messengers. - The insulin receptor is a tyrosine kinase enzyme that is activated by adding phosphates to several of its own tyrosines when insulin binds. - The activated insulin receptor provides docking sites for intracellular relay proteins that, in turn, initiate a series of protein phosphorylations that trigger specific cell responses

Parathyroid Hormone (PTH)

- PTH or parathormone, the protein hormone of these glands, is the single most important hormone controlling calcium balance in the blood. - Precise control of calcium levels is critical because Ca2+ homeostasis is essential for so many functions, including transmission of nerve impulses, muscle contraction, and blood clotting - Falling blood Ca2+ levels trigger PTH release, and rising blood Ca2+ levels inhibit its release. PTH increases Ca2+ levels in blood by stimulating three target organs: the skeleton, the kidneys, and the intestine - PTH release: 1. Stimulates osteoclasts (bone-resorbing cells) to digest some of the calcium-rich bony matrix and release ionic calcium and phosphates to the blood 2. Enhances the kidney's reabsorption of Ca2+ from the forming urine into the blood [and excretion of phosphate PO43−]. 3. Promotes activation of vitamin D, thereby increasing absorption of Ca2+ by intestinal mucosal cells. Vitamin D is required for absorption of Ca2+ from food, but first the kidneys must convert it to its active vitamin D3 form, calcitriol (1,25-dihydroxycholecalciferol). PTH stimulates this transformation

Factors that Influence Insulin Release

- Pancreatic beta cells secrete insulin when stimulated by: 1. Elevated blood glucose levels. This is the chief controlling factor. 2. Rising blood levels of amino acids and fatty acids 3. Acetylcholine released by parasympathetic nerve fibers 4. Hyperglycemic hormones (such as glucagon, epinephrine, growth hormone, thyroxine, or glucocorticoids). This effect is indirect and occurs because all of these hormones increase blood glucose levels - Somatostatin and sympathetic nervous system activation depress insulin release

The Endocrine System

- Plays a critical role in maintaining homeostasis - The body's "slow" chemical communication system; a set of glands that secrete hormones into the bloodstream - The endocrine system influences metabolic activity by means of hormones (hormone = to excite) - Hormones are chemical messengers secreted by cells into the extracellular fluids. - These messengers travel through the blood and regulate the metabolic function of other cells in the body - Binding of a hormone to cellular receptors initiates responses that typically occur after a lag period of seconds or even days---> But, once initiated, those responses tend to last much longer than those induced by the nervous system

Adrenal Glands

- Produce hormones involved in electrolyte balance and the stress response - The paired adrenal glands are pyramid-shaped organs perched atop the kidneys where they are enclosed in a fibrous capsule and a cushion of fat - They are also called the suprarenal glands (supra = above) - Each adrenal gland is structurally and functionally two endocrine glands. - The inner adrenal medulla, more like a knot of nervous tissue than a gland, is part of the sympathetic nervous system. - The outer adrenal cortex, encapsulating the medulla and forming the bulk of the gland, is glandular tissue derived from embryonic mesoderm - All adrenal hormones help us cope with stressful situations

Up-regulation and Down-regulation

- Receptors are dynamic structures. For example, persistently low levels of a hormone can cause its target cells to form additional receptors for that hormone. This is called up-regulation - Likewise, prolonged exposure to high hormone concentrations can decrease the number of receptors for that hormone. - This down-regulation desensitizes the target cells, so they respond less vigorously to hormonal stimulation, preventing them from overreacting to persistently high hormone levels - Hormones influence not only the number of their own receptors but also the number of receptors that respond to other hormones. - For example, progesterone down-regulates estrogen receptors in the uterus, thus antagonizing estrogens' actions. - On the other hand, estrogens cause the same cells to produce more progesterone receptors, enhancing their ability to respond to progesterone.

Regulation of Secretion

- Secretion of GH is regulated chiefly by two hypothalamic hormones with antagonistic effects 1. Growth hormone-releasing hormone (GHRH) stimulates GH release. Typically, GHRH, and therefore GH, secretion has a daily cycle with the highest levels occurring during evening sleep. The total amount secreted daily peaks during adolescence and then declines with age 2. Growth hormone-inhibiting hormone (GHIH), also called somatostatin inhibits GH release. GHIH release is triggered by the feedback of GH and IGFs. Rising levels of GH also feed back to inhibit its own release. GHIH is also produced in various locations in the gut, where it inhibits the release of virtually all gastrointestinal and pancreatic secretions—both endocrine and exocrine.

Pituitary Gland

- Securely seated in the sella turcica of the sphenoid bone, the tiny pituitary gland, or hypophysis secretes at least eight hormones - This gland is the size and shape of a pea on a stalk. Its stalk, the funnel-shaped infundibulum, connects the gland to the hypothalamus superiorly

Humoral Stimuli

- Some endocrine glands secrete their hormones in direct response to changing blood levels of certain critical ions and nutrients - These stimuli are called humoral stimuli - Humoral stimuli are the simplest endocrine controls. For example, cells of the parathyroid glands monitor the body's crucial blood Ca2+ levels and release parathyroid hormone as needed - Other hormones released in response to humoral stimuli include insulin (released in response to increased blood glucose) and aldosterone (released in response to low Na+ or high K+ blood levels)

How long does it take for a hormone to have an effect?

- Some hormones provoke target organ responses almost immediately, while others, particularly steroid hormones, require hours to days before their effects are seen. - Additionally, some hormones are secreted in a relatively inactive form and must be activated in the target cells - The duration of hormone action is limited, ranging from 10 seconds to several hours. - Effects may disappear rapidly as blood levels drop, or they may persist for hours even at very low levels. - Because of these many variations, hormonal blood levels must be precisely and individually controlled to meet the continuously changing needs of the body - Many characteristics of a hormone (such as its half-life and the time it takes to have an effect) depend on its solubility in water or lipids

Steroids

- Steroid hormones are synthesized from cholesterol - Only gonadal and adrenocortical hormones are steroids. - These hormones are all lipid soluble and can cross the plasma membrane

Hyperthyroidism

- Symptoms: elevated metabolism, sweating, rapid heartbeat, nervousness, weight loss - Common cause is Graves' disease---> autoimmune disorder in which the body makes abnormal antibodies that mimic the action of TSH on follicular cells of the thyroid - This causes the thyroid to be stimulated and produce a goiter - TSH levels are low when a tumor is present and there is no goiter

Thyroid-Stimulating Hormone (TSH)

- TSH, or thyrotropin, is a tropic hormone that stimulates normal development and secretory activity of the thyroid gland. Its release follows the hypothalamic-pituitary-target endocrine organ feedback loop - The hypothalamic peptide thyrotropin-releasing hormone (TRH) triggers the release of TSH from thyrotropic cells of the anterior pituitary which then stimulates the thyroid gland to produce thyroxine - Rising blood levels of thyroid hormones act on both the pituitary and the hypothalamus to inhibit TSH secretion. - GHIH also inhibits TSH secretion

The Adrenal Cortex

- The adrenal cortex synthesizes well over two dozen steroid hormones, collectively called corticosteroids - The multistep steroid synthesis pathway begins with cholesterol, and involves varying intermediates depending on the hormone being formed. - Unlike the amino acid-based hormones, steroid hormones are not stored in cells. - Consequently, their rate of release depends on their rate of synthesis

How does a hormone communicate with its target cell?

- The answer depends on the chemical nature of the hormone and the cellular location of the receptor. - Hormones act at receptors in one of two ways: 1. Water-soluble hormones (all amino acid-based hormones except thyroid hormone) act on receptors in the plasma membrane. - These receptors are usually coupled via regulatory molecules called G proteins to one or more intracellular second messengers, which mediate the target cell's response 2. Lipid-soluble hormones (steroid and thyroid hormones) act on receptors inside the cell, which directly activate genes - Receptors for water-soluble hormones must be in the plasma membrane since these hormones cannot diffuse across the plasma membrane, and receptors for lipid-soluble steroid and thyroid hormones are inside the cell because these hormones can diffuse across the plasma membrane into the cell

Anterior Pituitary Hormones

- The anterior pituitary releases six hormones, all of them peptides or proteins—growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) - When the anterior pituitary receives an appropriate chemical stimulus from the hypothalamus, it releases one or more of its hormones - Four of the six anterior pituitary hormones—thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone—are tropic hormones or tropins that regulate the secretory action of other endocrine glands - All anterior pituitary hormones except growth hormone affect their target cells via a cyclic AMP second-messenger system

Location and Structure

- The butterfly-shaped thyroid gland is located in the anterior neck, on the trachea just inferior to the larynx - A median tissue mass called the isthmus (is′mus) connects its two lateral lobes - The thyroid gland is the largest pure endocrine gland in the body - Internally, the gland is composed of hollow, spherical follicles - The walls of each follicle are formed largely by cuboidal or squamous epithelial cells called follicular cells, which produce the glycoprotein thyroglobulin - The central cavity, or lumen, of the follicle stores colloid, an amber-colored, sticky material consisting of thyroglobulin molecules with attached iodine atoms. Thyroid hormone is derived from this iodinated thyroglobulin - The parafollicular cells, another population of endocrine cells in the thyroid gland, produce calcitonin

Actions

- The dramatically higher output of glucocorticoids during stress is essential for negotiating the crisis. - Cortisol provokes a marked rise in blood levels of glucose, fatty acids, and amino acids. - Cortisol's prime metabolic effect is to provoke gluconeogenesis, that is, the formation of glucose from fats and proteins - Under cortisol's influence, proteins are broken down to provide building blocks for repair or to make enzymes for metabolic processes. - Cortisol's second critical function is to enhance the sympathetic nervous system's vasoconstrictive effects, helping to maintain blood pressure - Note that ideal amounts of glucocorticoids promote normal function, but too much cortisol exerts significant anti-inflammatory and anti-immune effects. Excessive levels of glucocorticoids: 1. Depress cartilage and bone formation 2. Inhibit inflammation by decreasing the release of inflammatory chemicals 3. Depress the immune system 4. Disrupt normal cardiovascular, neural, and gastrointestinal function

Mineralocorticoids

- The essential function of mineralocorticoids is to regulate the electrolyte (mineral salt) concentrations in extracellular fluids, particularly of Na+ and K+ - The single most abundant cation in extracellular fluid is Na+, and the amount of Na+ in the body largely determines the volume of the extracellular fluid—where Na+ goes, water follows. - Changes in Na+ concentration lead to changes in blood volume and blood pressure. - The extracellular concentration of K+ is also critical—it sets the resting membrane potential of all cells and determines how easily action potentials are generated in nerve and muscle. - Na+ and K+ regulation are crucial to overall body homeostasis. - Their regulation is the primary job of aldosterone the most potent mineralocorticoid. - Aldosterone accounts for more than 95% of the mineralocorticoids produced and is essential for life. - Aldosterone reduces excretion of Na+ from the body. - Its primary target is the kidney tubules, where it: 1. Stimulates Na+ reabsorption (causing increased blood volume and blood pressure because water follows Na+) 2. Causes K+ secretion into the tubules for elimination from the body - Decreasing blood volume and blood pressure, and rising blood levels of K+, stimulate aldosterone secretion. - The reverse conditions inhibit its secretion. - Four mechanisms regulate aldosterone secretion, but two of them—the renin-angiotensin-aldosterone mechanism and plasma concentrations of potassium—are by far the most important

The Gonads

- The male and female gonads (testes and ovaries) produce steroid sex hormones identical to those produced by adrenal cortical cells - The major distinction is the source and relative amounts produced - The paired ovaries are small, oval organs located in the female's abdominopelvic cavity. - Besides producing ova, or eggs, the ovaries produce several hormones, most importantly estrogens and progesterone - Estrogens are responsible for maturation of the reproductive organs and the appearance of the secondary sex characteristics of females at puberty - Estrogen also stimulates bone growth and protection against osteoporosis (reduction in bone quality and density) - After menopause, the ovaries stop producing and secreting estrogen and a loss of bone density follows which can result in osteoporosis - Acting with progesterone, estrogens promote breast development and cyclic changes in the uterine mucosa (the menstrual cycle) - The male testes, located in an extra-abdominal skin pouch called the scrotum, produce sperm and male sex hormones, primarily testosterone - During puberty, testosterone initiates the maturation of the male reproductive organs and the appearance of secondary sex characteristics and sex drive. - In addition, testosterone is necessary for normal sperm production and maintains the reproductive organs in their mature functional state in adult males

Nervous System Modulation

- The nervous system can modify both "turn-on" factors (hormonal, humoral, and neural stimuli) and "turn-off" factors (feedback inhibition and others) that affect the endocrine system - In your body, it is the nervous system that makes certain adjustments to maintain homeostasis by overriding normal endocrine controls. - For example, the action of insulin and several other hormones normally keeps blood glucose levels in the range of 90-110 mg/100 ml of blood. - However, when your body is under severe stress, blood glucose levels rise because the hypothalamus and sympathetic nervous system centers are strongly activated. - In this way, the nervous system ensures that body cells have sufficient fuel in case vigorous activity is required.

The Pineal Gland

- The pineal gland secretes melatonin - The tiny, pinecone-shaped pineal gland hangs from the roof of the third ventricle in the diencephalon - Its secretory cells, called pinealocytes, are arranged in compact cords and clusters - Its only major secretory product is melatonin an amine hormone derived from serotonin - Melatonin concentrations in the blood rise and fall in a diurnal (daily) cycle. - Peak levels occur during the night and make us drowsy, and lowest levels occur around noon. - Recent evidence suggests that melatonin also controls the production of protective antioxidant and detoxification molecules within cells. - The suprachiasmatic nucleus of the hypothalamus, an area referred to as our "biological clock," is richly supplied with melatonin receptors, and exposure to bright light (known to suppress melatonin secretion) can reset the clock timing. - As a result, changing melatonin levels may influence rhythmic variations in physiological processes such as body temperature, sleep, and appetite.

The Placenta

- The placenta is a temporary endocrine organ. - Besides sustaining the fetus during pregnancy, it secretes several steroid and protein hormones that influence the course of pregnancy. - Placental hormones include estrogens, progesterone, and human chorionic gonadotropin (hCG)

The Posterior Pituitary and Hypothalamic Hormones

- The posterior pituitary consists largely of axon terminals of hypothalamic neurons whose cell bodies are located in the supraoptic or paraventricular nuclei - The paraventricular neurons primarily make oxytocin - and the supraoptic neurons mainly produce antidiuretic hormone (ADH) - Axon terminals in the posterior pituitary release these hormones "on demand" in response to action potentials that travel down the axons of these same hypothalamic neurons - Acts as a storage area for these neurohormones

The Renin-Angiotensin-Aldosterone Mechanism

- The renin-angiotensin-aldosterone mechanism influences both blood volume and blood pressure by regulating the release of aldosterone and therefore Na+ and water reabsorption by the kidneys. 1. When blood pressure (or blood volume) falls, specialized cells of the juxtaglomerular complex in the kidneys are excited. 2. These cells respond by releasing renin into the blood 3. Renin splits off part of the plasma protein angiotensinogen, triggering an enzymatic cascade that forms angiotensin II, which stimulates the glomerulosa cells to release aldosterone

Skin

- The skin produces cholecalciferol, an inactive form of vitamin D3, when modified cholesterol molecules in epidermal cells are exposed to ultraviolet radiation - This compound then enters the blood via the dermal capillaries, is modified in the liver, and becomes fully activated in the kidneys - The active form of vitamin D3, calcitriol, is an essential regulator of the carrier system that intestinal cells use to absorb Ca2+ from food. - Without this vitamin, bones become soft and weak. - In addition, most cells throughout the body have vitamin D receptors. - Vitamin D modulates immune functions, decreases inflammation, and may act as an anticancer agent

The Adrenal Medulla

- The spherical medullary chromaffin cells, which crowd around porous blood-filled capillaries, are modified postganglionic sympathetic neurons. - The cells synthesize the catecholamines epinephrine and norepinephrine (NE) via a molecular sequence from tyrosine to dopamine to NE to epinephrine - When a short-term stressor activates the body to fight-or-flight status, the sympathetic nervous system is mobilized. - Blood vessels constrict and the heart beats faster (together raising the blood pressure), and blood is diverted from temporarily nonessential organs to the heart and skeletal muscles. Blood glucose levels rise, and preganglionic sympathetic nerve endings weaving through the adrenal medulla signal for release of catecholamines, which reinforce and prolong the fight-or-flight response - Epinephrine is the more potent stimulator of metabolic activities and dilator of small airways (bronchioles), but norepinephrine has a greater influence on peripheral vasoconstriction and blood pressure. - Epinephrine is used clinically as a heart stimulant and to dilate the bronchioles during acute asthmatic attacks and severe allergic reactions - Unlike hormones from the adrenal cortex, which promote long-lasting body responses to stressors, catecholamines cause fairly brief responses

Hormones are regulated by what type of feedback mechanism?

- The synthesis and release of most hormones are regulated by some type of negative feedback mechanism. - In such a mechanism, some internal or external stimulus triggers hormone secretion. - As levels of a hormone rise, it causes target organ effects, which then feed back to inhibit further hormone release. - As a result, blood levels of many hormones vary only within a narrow range

Synthesis

- The thyroid gland is unique among the endocrine glands in its ability to store its hormone extracellularly and in large quantities. A normal thyroid gland stores enough colloid to provide normal levels of hormone for two to three months - When TSH from the anterior pituitary binds to receptors on follicular cells, their first response is to secrete stored thyroid hormone. Their second response is to begin synthesizing more colloid to "restock" the follicle lumen - As a general rule, TSH levels are lower during the day, peak just before sleep, and remain high during the night - The blood carries TSH to its target tissue, the thyroid gland. TSH causes the thyroid gland to increase in size and secrete thyroxine into the general circulation - The hypothalamic peptide thyrotropin-releasing hormone (TRH) triggers the release of TSH from thyrotropic cells of the anterior pituitary which then stimulates the thyroid gland to produce thyroxine Negative Feedback Mechanism - When circulation levels of thyroxine are low, the hypothalamus secretes more TRH to stimulate the pituitary gland to secrete more TSH which increases the secretion of thyroxine in the thyroid gland---> this will then influence the hypothalamus to reduce its production of TRH - Rising blood levels of thyroid hormones act on both the pituitary and the hypothalamus to inhibit TSH secretion. - If TSH levels are too high, the thyroid gland enlarges---> the resulting glandular swelling is called a goiter

The Cyclic AMP Signaling Mechanism

- This mechanism involves the interaction of three plasma membrane components—a hormone receptor, a G protein, and an effector enzyme (adenylate cyclase)—to determine intracellular levels of cyclic AMP STEP 1: Hormone binds receptor - The hormone, acting as the first messenger, binds to its receptor in the plasma membrane STEP 2: Receptor activates G protein - Hormone binding causes the receptor to change shape, allowing it to bind a nearby inactive G protein. - This in turn allows the G protein to be activated as the guanosine diphosphate (GDP) bound to it is displaced by the high-energy compound guanosine triphosphate (GTP). - The G protein behaves like a light switch: It is "off" when GDP is bound to it, and "on" when GTP is bound STEP 3: G protein activates adenylate cyclase - The activated G protein (moving along the membrane) binds to the effector enzyme adenylate cyclase. Some G proteins (Gs) stimulate adenylate cyclase - Other (Gi) inhibit adenylate cyclase - Eventually, the GTP bound to the G protein is hydrolyzed to GDP and the G protein becomes inactive once again STEP 4: Adenylate cyclase converts ATP to cyclic AMP - For as long as activated Gs is bound to it, adenylate cyclase generates the second messenger cAMP from ATP STEP 5: Cyclic AMP activates protein kinases - cAMP, which is free to diffuse throughout the cell, triggers a cascade of chemical reactions by activating protein kinases - Protein kinases are enzymes that phosphorylate (add a phosphate group to) various proteins, many of which are other enzymes. - Because phosphorylation activates some of these proteins and inhibits others, it may affect a variety of processes in the same target cell at the same time

Insulin and Glucagon from pancreas regulate blood glucose levels

16.7

Pituitary-Hypothalamic Relationships

POSTERIOR LOBE - The posterior lobe is actually part of the brain. It derives from hypothalamic tissue that grows downward, maintaining its neural connection with the hypothalamus via a bundle of axons called the hypothalamic-hypophyseal tract. - This tract runs through the infundibulum - This tract arises from neurons in the paraventricular and supraoptic nuclei of the hypothalamus - These neurosecretory cells synthesize one of two neurohormones and transport them along their axons to the posterior pituitary. - When these hypothalamic neurons fire, they release the stored hormones into a capillary bed in the posterior pituitary for distribution throughout the body ANTERIOR LOBE - There is no direct neural connection between the anterior lobe and hypothalamus, but there is a vascular connection. - Specifically, the primary capillary plexus in the infundibulum communicates inferiorly via the small hypophyseal portal veins with a secondary capillary plexus in the anterior lobe - The primary and secondary capillary plexuses and the intervening hypophyseal portal veins make up the hypophyseal portal system - Via the hypophyseal portal system, releasing and inhibiting hormones secreted by neurons in the ventral hypothalamus circulate to the anterior pituitary, where they regulate secretion of its hormones - All these hypothalamic regulatory hormones are amino acid based, but they vary in size from a single amine to peptides to proteins

Steps on how follicular cells synthesize thyroid hormone

STEP 1: Thyroglobulin is synthesized and discharged into the follicle lumen - After being synthesized on the ribosomes of the follicular cell's rough endoplasmic reticulum, thyroglobulin is transported to the Golgi apparatus, where sugar molecules are attached and the thyroglobulin is packed into transport vesicles. - These vesicles move to the apex of the follicular cell, where they discharge their contents into the follicle lumen to become part of the stored colloid STEP 2: Iodide is trapped - To produce the functional iodinated hormones, the follicular cells must accumulate iodides (anions of iodine, I−) from the blood - Once trapped inside the follicular cell, iodide then moves into the follicle lumen by facilitated diffusion STEP 3: Iodide is oxidized to iodine - At the border of the follicular cell and colloid, iodides are oxidized (by removal of electrons) and converted to iodine I2. STEP 4: Iodine is attached to tyrosine - Iodine is attached to tyrosine amino acids that are part of the thyroglobulin molecule - Attachment of one iodine to a tyrosine produces monoiodotyrosine (MIT), and attachment of two iodines produces diiodotyrosine (DIT) STEP 5: Iodinated tyrosines are linked together to form T3 and T4 - Enzymes in the colloid link MIT and DIT together. Two linked DITs result in T4, and coupling of MIT and DIT produces T3 STEP 6: Thyroglobulin colloid is endocytosed - To secrete the hormones, the follicular cells must reclaim iodinated thyroglobulin by endocytosis and combine the vesicles with lysosomes STEP 7: Lysosomal enzymes split T4 and T3 from thyroglobulin and the hormones diffuse from the follicular cell into the bloodstream - The main hormonal product secreted is T4. Some T4 is converted to T3 before secretion, but most T3 is generated in the peripheral tissues