Chapter 16: Endocrine System

Lipid-Soluble Hormones Mechanism of Action at Target Cell

Activates genes, causing synthesis of new proteins

Sources of Lipid-Soluble Hormones

Adrenal cortex, gonads, and thyroid gland

ACTH Target Organ and Effects

Adrenal cortex: promotes release of glucocorticoids and androgens (mineralocorticoids to a lesser extent)

Examples of Water-Soluble Hormones

All amino-acid based hormones except thyroid hormone

Sources of Water-Soluble Hormones

All endocrine glands except adrenal cortex, gonads and thyroid gland

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 cell are its target cells.

Examples of Lipid-Soluble Hormones

All steroid hormones and thyroid hormones

Endocrine Glands

Also called ductless glands. Produce hormones and lack ducts. They release their hormones into 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.

Major Growth Hormone Targets

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.

What does target cell activation depend on?

Although binding of a hormone to a receptor is the crucial first step, target cell activation depends equally on three other factors: 1. Blood levels of the hormone 2. Relative numbers of receptors for the hormone on or in the target cell 3. Affinity (strength) of the binding between the hormone and the receptor.

How does Antagonism Occur?

Antagonists may compete for the the same receptors, act through different metabolic pathways, or even cause down-regulation of the receptors for the antagonistic hormone.

Example of Synergism

Both glucagon and epinephrine cause the liver to release glucose in the blood. When they act together, the amount of glucose released is about 150% of what is released when each hormone acts alone.

How are Lipid-Soluble Hormones Transported in the Blood?

Bound to plasma proteins

PRL's target organ and effects

Breast secretory tissue: promotes lactation

Humoral Stimuli Examples

Cells of the parathyroid glands monitor the body's crucial blood calcium levels and release parathyroid hormones 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+ (sodium) or high K+ (potassium) blood levels)

What feedback mechanism cause childbirth and milk ejection?

Childbirth and milk ejection result from positive feedback mechanism

Effect of hyposecretion of TSH

Cretinism in children and myxedema in adults

Effects of hypersecretion of ACTH

Cushing's Disease

Effects of Hyposecretion of ADH

Diabetes Insipidus

Cause of Diabetes Insipidus

Diabetes Insipidus can be caused by a blow to the head that damages the hypothalamus or the posterior pituitary. Though inconvenient, the condition is not serious when thirst center is operating properly and the person drinks enough water to prevent dehydration. However, it can be life threatening in unconscious or comatose patients and is a reason why accident victims with head trauma must be carefully monitored.

Diabetes Insipidus

Diabetes Insipidus is the result of ADH deficiency. Diabetes Insipidus is a syndrome marked by intense thirst and huge urine output. The name of the condition (diabetes = overflow; insipidus = tasteless) distinguishes it from diabetes mellitus (mel = honey), in which insulin deficiency causes large amounts of blood glucose to be lost in the urine.

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.

List of Endocrine Glands

Endocrine glands include the pituitary, thyroid, adrenal and pineal glands. The hypothalamus, along with its neural functions, produces and releases hormones, so we can consider the hypothalamus a neuroendocrine organ. In addition, several organs, such as the pancreas, gonads (ovaries and testes), and placenta, contain endocrine tissue. Most other organs also contain scattered endocrine cells or small cluster of endocrine cells.

Hormonal Stiumuli

Endocrine glands release their hormones in response to hormones produced by other endocrine organs. Hormonal stimuli promote rhythmic hormone release, with hormone blood levels rising and falling in a specific pattern.

What is FSH inhibited by?

FSH is inhibited by feedback inhibition exerted by inhibin, and estrogens in females and testosterone in males

What is FSH stimulated by?

FSH is stimulated by GnRH+

Effect of Hyposecretion of FSH

Failure of sexual maturation

Effect of Hyposectretion of LH

Failure of sexual maturation

Insulin-Like Growth Factors (IGFs)

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).

What triggers the release of Growth Hormone-Inhibiting Hormone?

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.

Effects of Hypersecretion of Growth Hormone

Gigantism in children and acromegaly in adults

Follicle-Stimulating Hormone (FSH) Chemical Structure and Cell Type

Glycoprotein, gonadotropic cells

Luteinizing Hormone (LH) Chemical Structure and Cell Type

Glycoprotein, gonadotropic cells

Thyroid-Stimulating Hormone (TSH) Chemical Structure and Cell Type

Glycoprotein, thyrotropic cells

What Hormones are Produced by the Anterior Pituitary Gland?

Growth Hormone (GH) Thyroid-Stimulating Hormone (TSH) Adrenocorticotropic Hormone (ACTH) Follicle-Stimulating Hormone (FSH) Luteinizing Hormone (LH) Prolactin Hormone (PRL) **All six anterior pituitary hormones are peptides or proteins.

What is Growth Hormone Inhibited by?

Growth Hormone is inhibited by feedback inhibition exerted by GHs and IGFs, and by hyperglycemia, hyperlipidemia, obesity, and emotional deprivation via either increases GHIH (somatostatin) or decreased GHRH+ release

What is Growth Hormone Stimulated by?

Growth Hormone is stimulated by GHRH+ release, which is triggered by low blood levels of GH as well as by a number of secondary triggers, including hypoglycemia, increases in blood levels of amino acids, low levels of fatty acids, exercise, and other types of stressors

Difference between hormones and autocrines and panacrines

Hormones are long-distance chemical signals that travel in blood or lymph throughout the body. Autocrines and paracrines, on the other hand, are short-distance signals. Autocrines are chemicals that exert their effects on the same cell that secretes them. Panacrines also act locally (within the same tissue) but affect cell types other than those releasing the paracrine chemicals.

How do hormones circulate in the blood?

Hormones circulate in the blood in two forms - free or bound to a protein carrier. In general, lipid-soluble hormones (steroid and thyroid hormone) travel in the bloodstream attached to plasma proteins. Most others circulate without carriers.

Syndrome of Inappropriate ADH Secretion (SIADH)

Hypersecretion of ADH can occur in children with meningitis, or in adults who have neurosurgery, hypothalamic injury, or cancer (particularly lung cancer) in which cancer cells are additional sources of ADH. It also may occur after general anesthesia or administration of certain drugs. The resulting condition, Syndrome of Inappropriate ADH Secretion (SIADH) is marked by the retention of fluid, headache and disorientation due to brain edema, weight gain and decreased solute concentration in the blood. SIADH management requires restricting fluids and carefully monitoring blood sodium levels.

How does the hypothalamus control the release of hormones from the anterior pituitary gland?

Hypothalamic hormones released into special blood vessels (the hypophyseal portal system) control the release of anterior pituitary hormones.

Effect of hypersecretion of TSH

Hypothyroidism; effects similar to those of Grave's disease, in which antibodies mimic TSH

What actions required for growth are stimulated by IGFs?

IGFs stimulate actions required for growth: - Uptake of nutrients from the blood and their incorporation into proteins and DNA, allowing growth by cell division - Formation of collagen and deposition of bone matrix

Effect of Hypersecretion of PRL

Inappropriate milk production (galacctorrhea); cessation of menses in females; impotence in males

What is PRL inhibited by?

Inhibited by PIH (dopamine)

Example of Antagonism

Insulin, which lowers blood glucose levels, is antagonized by glucagon, which raises blood glucose levels.

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

It varies. Some hormones provoke target organ response almost immediately, while others, particularly steroid hormones, require hours to day before their effects are seen. Additionally, some hormones are secreted in a relatively inactive form and must be activated in the target cells.

What are ADH's target organ and effects?

Kidneys: stimulate kidney tubule cells to reabsorb water

What is LH inhibited by?

LH is inhibited by feedback inhibition exerted by estrogens and progesterone in females and testosterone in males

What is LH stimulated by?

LH is stimulated by GnRH+

How do lipid-soluble hormones communicate with their target cells?

Lipid-soluble hormones (steroid and thyroid hormones) act of receptors inside the cell, which directly activate genes.

Growth Hormone Target Organ and Effects

Liver, muscle, bone, cartilage and other tissues: anabolic hormone; stimulates somatic growth, mobilizes fat, spares glucose Growth-promoting effects mediated indirectly by IGFs

Lipid-Soluble Hormones Half-Lives in Blood

Long (most need to be metabolized by the liver)

Amino Acid Based Hormones

Most hormones are amino acid based. Molecular size varies widely in this group - from simple amino acid derivatives (which include biogenic amines), 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.

Neural Stimuli

Nerve fibers stimulate hormone release

Can Lipid-Soluble Hormones be Stored in Secretory Vesicles?

No

Effect of Hypersecretion of LH

No important effects

Effect of Hypersectretion of FSH

No important effects

Synergism

Occurs when more than one hormone produces the same effects at the target cell and their combined effects are amplified.

Antagonism

Occurs when one hormone opposes the action of another.

Location of Receptors for Water-Soluble Hormones

On plasma membrane

LH's target organ and effect

Ovaries and testes: in females triggers ovulation and stimulates ovarian production of estrogens and progesterone; in males promotes testosterone production

FSH's target organs and effects

Ovaries and testes: in females, stimulates ovarian follicle maturation and production of estrogens; in males, stimulates sperm production

How does oxytocin act?

Oxytocin acts via the PIP2-CA2+ second-messenger system to mobilize CA2+, allowing stronger contractions.

What are oxytocin and ADH composed of?

Oxytocin and ADH are each composed on nine amino acids and are almost identical. They differ in only two amino acids, and yet have dramatically different physiological effects.

What hormones are made by the hypothalamic neurons and stored in the posterior pituitary?

Oxytocin and Antidiuretic Hormone (ADH)

What is oxytocin inhibited by?

Oxytocin is inhibited by lack of appropriate neural stimuli.

What is oxytocin stimulated by?

Oxytocin is stimulated by impulses from hypothalamic neurons in response to cervical/uterine stretching and sucking of infant at breast. Oxytocin is released in significantly higher amounts during childbirth and in nursing women.

What is PRL stimulated by?

PRL is stimulated by decreased PIH; release enhanced by estrogens, birth control pills, breast-feeding, and dopamine-blocking drugs

Adrenocorticotropic Hormone (ACTH) Chemical Structure and Cell Type

Peptide, corticotropic cells

Oxytocin Chemical Structure and Cell Type

Peptide, mostly from neurons in paraventricular nucleus of hypothalamus

What are the three types of hormone interaction?

Permissiveness, Synergism, Antagonism

Up-Regulation

Persistently low levels of a hormone can cause its target cells to form additional receptors for that hormone.

Effects of Hyposecretion of Growth Hormone

Pituitary Dwarfism in Children

Effect of Hyposecretion of PRL

Poor milk production in nursing women

Exocrine Glands

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

Down-Regulation

Prolonged exposure to high hormone concentrations can decrease the number of receptors for that hormone. Down-regulation desensitizes the target cells, so they respond less vigorously to hormonal stimulation, preventing them from overreacting to persistently high hormone levels.

Growth Hormone Chemical Structure and Cell Type

Protein, Somatotropic Cells

Prolactin (PRL) Chemical Structure and Cell Type

Protein, prolactin cells

Effects of hyposecretion of ACTH

Rare

Receptors for Water-Soluble Hormones vs. Receptors for Lipid-Soluble Hormones

Receptors for water-soluble hormones must be in the plasma membrane since these hormones cannot enter the cell, and receptors for lipid-soluble steroid and thyroid hormones are inside the cell because these hormones can enter the cell.

Tropic Hormones or Tropins

Regulate the secretory action of other endocrine glands. Four of the six anterior pituitary hormones are tropic hormones or tropins: 1. Thyroid-Stimulating Hormone 2. Adrenocorticotropic Hormone 3. Follicle-Stimulating Hormone 4. Luteinizing Hormone

Hormonal Stimuli Examples

Releasing and inhibiting hormones produced the 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 increases, they inhibit the release of anterior pituitary hormones and thus their own release.

Example of Permissiveness

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.

Regulation of Growth Hormone Secretion

Secretion of GH is regulated chiefly by two hypothalamic hormones with antagonistic effects. Growth Hormone-Releasing Hormone (GHRH) stimulates GH release, while Growth Hormone-Inhibiting Hormone (GHIH) also called somatostatin inhibits it. Recent research shots that the "hunger hormone" ghrelin (produced by the stomach) also stimulates GH release.

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, funnel-shaped infundibulum connects the gland to the hypothalamus superiorly.

Water-Soluble Hormones Half-Lives in Blood

Short (most can be removed by kidneys)

Permissiveness

Situation in which one hormone cannot exert its full effect without another hormone being present.

Growth Hormone

Somatropic 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.

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.

Steroid Hormones

Steroid Hormones are synthesized from cholesterol. Of the hormones produced by the major endocrine organs, only gonadal and adrenocortical hormones are steroids. These hormones are all lipid soluble and can cross the plasma membrane.

Effects of Hypersecretion of ADH

Syndrome of inappropriate ADH secretion (SIADH)

What is TSH inhibited by?

TSH is inhibited by feedback inhibition exerted by thyroid hormones on anterior pituitary and hypothalamus and by GHIH

What is TSH stimulated by?

TSH is stimulated by TRH+ and in infants indirectly by cold temperature

Example of Nervous System Modulation

The action of insulin and several other hormones normally keeps blood glucose levels in the rage of 90-110/mg/100ml 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 his way, the nervous system ensures that body cells have sufficient fuel in case vigorous activity is required.

Anterior Pituitary Hormones

The anterior pituitary has traditionally been called the "master endocrine gland" because many of the numerous hormones it produces regulate the activity of other endocrine glands. In recent years, however, it has been dethroned by the hypothalamus, which is now known to control the activity of the anterior pituitary. When the anterior pituitary receives an appropriate chemical stimulus from the hypothalamus, it releases one or more of its hormones.

Anterior Pituitary Lobe

The anterior pituitary love or adenohypophysis is composed of glandular tissue. It manufactures and releases a number of hormones.

Neural Stimuli Examples

The classic example of neural stimuli is in response to stress, in which the sympathetic nervous system stimulates the adrenal medulla to release norepinephrine and epinephrine.

What does the concentration of a circulating hormone in the blood reflect?

The concentration of a circulating hormone in blood at any time reflects: 1. its rate of release and 2. the speed at which it is inactivated and removed from the body.

What is the duration of hormone action?

The duration of hormone action is limited, ranging from 10 seconds to several hours.

Hormones stored in the posterior pituitary gland

The hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). The oxytocin and ADH are then transported down the axons of the hypothalamic-hypophyseal tract to the posterior pituitary when they are stored in axon terminals. When associated hypothalamic neurons fire, action potentials arriving at the axon terminal cause oxytocin or ADH to be released into the blood.

Half-Life

The length of time for a hormone's blood level to decrease by half. A hormones half-life varies from a fraction of a minute to a week. Water-soluble hormones have the shortest half-lives.

Nervous System Modulation

The nervous system can modify both "turn-on" factors (hormonal, humeral and neural stimuli) and "turn-off" factors (feedback inhibition and others) that affect the endocrine system. It is the nervous system that makes certain adjustments to maintain homeostasis by overriding normal endocrine controls.

Oxytocin

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 uterus and cervix as birth nears dispatches afferent impulses to the hypothalamus. The hypothalamus response by synthesizing oxytocin and triggering its release from the posterior pituitary.

Hypothalamic-Hypophyseal Tract

The posterior lobe is actually part of the brain. It derives from a down growth of the hypothalamic tissue and maintains its neural connection with the hypothalamus via a nerve bundle called the hypothalamic-hypophyseal tract, which runs through the infundibulum.

Neurohypophysis

The posterior lobe plus the infundibulum

Two Major Lobes of the Pituitary Gland in Humans

The posterior pituitary and the anterior pituitary

Posterior Pituitary Lobe

The posterior pituitary lobe is composed larges of neural tissue such as pituicytes and nerve fibers. It releases neurohormones (hormones secreted by neurons) received ready-made from the hypothalamus. The posterior pituitary lobe is a hormone-storage area and not a true endocrine gland that manufactures hormones.

Negative 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.

Three types of stimuli that cause hormone release

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

What is TSH's target organ and effects?

Thyroid gland: stimulates thyroid gland to release thyroid hormones

Growth Hormone Secretion Cycle

Typically, 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.

Effects of hyposecretion or hypersectretion of oxytocin?

Unknown

Water-Soluble Hormones Mechanism of Action at Target Cell

Usually act through second-messenger systems

How are Water-Soluble Hormones Transported in Blood?

Usually free in plasma

Location of Receptors for Lipid-Soluble Hormones

Usually inside cell

What are oxytocin's target organs and effects?

Uterus: stimulates uterine contractions; initiates labor Breast: Initiates milk ejection

How do water-soluble hormones communicate with target their target cells?

Water-soluble hormones (all amino-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.

Can Water-Soluble Hormones be Stored in Secretory Vesicles?

Yes

The Cyclic AMP Signaling Mechanism

1. Hormone Binds Receptor 2. Receptor Activates G Protein 3. G Protein Activates Adenylate Cyclase 4. Adenylate Cyclase Converts ATP to Cyclic AMP 3. Cyclic AMP Activates Protein Kinases

Direct Gene Activation Mechanism of Lipid-Soluble Hormones

1. The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor 2. The receptor hormone complex enters the nucleus 3. The receptor-hormone complex binds a specific DNA region 4. Binding initiates transcription of the gene to mRNA 5. The mRNA directs protein synthesis.

What changes does a hormone typically produce?

A hormone typically 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 does a hormone's chemical structure determine?

A hormone's chemical structure determines its solubility in water. Its water solubility in turn affects how the hormone is transported in the blood, low 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 as either amino acid based or steroids.

What is ACTH inhibited by?

ACTH is inhibited by feedback inhibition exerted by glucocorticoids

What is ACTH stimulated by?

ACTH is stimulated by CRH+; stimuli that increase CRH release include fever, hypoglycemia and other stressors

Antidiuretic Hormone (ADH) Chemical Structure and Cell Type

ADH (also called vasopressin) is composed on peptides, mostly from neurons in supraoptic nucleus of hypothalamus

What is ADH inhibited by?

ADH is inhibited by adequate hydration of the body and by alcohol (drinking lots of water inhibits ADH release)

What is ADH stimulated by?

ADH is stimulated by impulses from the hypothalamic neurons in response to increased blood solute concentration or decreased blood volume; also stimulated by pain, some drugs and low blood pressure.

Growth Hormone's Direct Actions of Metabolism

Acting directly, GH exerts metabolic effects. It mobilizes fat 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.

How does the hypothalamus control the release of hormones from the posterior pituitary gland?

Action potentials travel down the axons of hypothalamic neurons, causing hormone release from their own axon terminals in the posterior pituitary.