Chapter 16: The Endocrine System Learning Objectives

Hypersecretion of GH

usually due to pituitary tumor) results in gigantism (if it occurs before epiphyseal plate closure); if it occurs after plate closure, the result is acromegaly, meaning enlarged extremities, particularly bones of the hands, feet, and face.

At high concentrations, ADH acts as a

vasoconstrictor, so is also known as vasopressin.

Low blood pressure also stimulates ADH release

while excessive water intake inhibits its release.

Oxytocin also known as?

"cuddling hormone" and promotes nurturing, couple bonding, and trust

Hypersecretion of aldosterone:

(e.g. Conn's disease) result is hypertension and edema due to water retention and hypokalemia resulting in muscle weakness and reduced neuronal excitability.

N.B. Eicosanoids

(leukotrienes and prostaglandins) generally act as paracrines or autocrines and don't fit true definition of hormones

Describe the mechanism of protein and peptide hormone action by signal transduction involving PM receptors and second messengers; include G proteins

-Amino acid based hormones (except thyroid hormone) are water soluble and incapable of crossing the plasma membrane (PM). Therefore, they must bind to PM receptors, which are coupled to G proteins. When hormone (first messenger) binds to a PM receptor, the G-protein coupled to the receptor becomes activated by acquiring GTP. The activated G-protein binds to the effector enzyme, adenylate cyclase, and can activate (Gs) or inhibit (Gi) it.

Describe the chemical classification of hormones (2 chemical classifications of hormones):

-amino acid based: peptides, proteins, and amino acid derivatives (e.g. pituitary hormones) -steroids: synthesized from cholesterol, mainly gonadal and adrenocortical hormones

Define Hormone

-hormones are chemical messengers secreted by cells into the extracellular fluid -hormones travel through the blood to regulate metabolic functions in target organs

GH stimuli: Growth Hormone

-low blood sugar, low blood GH levels, increase in blood levels of amino acids, low blood free fatty acid levels, exercise, and other stressors -inhibited by GHIH -GH release follows a daily cycle with highest levels during sleep

Growth Hormone (GH Effects)

-promotes lipolysis to supply free fatty acids for fuel -stimulates liver to break down glycogen and release glucose to blood -inhibits glucose uptake and metabolism -increases amino acid uptake into cells, for incorporation into proteins Indirectly via insulin-like growth factor (IGF): cellular uptake of nutrients for protein and DNA synthesis for growth by cell division; formation of collagen and deposition of bone matrix -major targets are bone growth and increase in skeletal muscle mass

Parathyroid Hormones Effects

-stimulating hydroxylation of Vit. D (calcitriol) to active form in the kidney; calcitriol is necessary for absorption of Ca2+ from diet in the gut -promoting Ca2+ reabsorption and Phosphate excretion in kidney -stimulating activation of osteoclasts in bone to resorb bone and release Ca2+ into blood

Heart

ANP-decreases Na+ and water retention, inhibits RAAS.

Adenylate cyclase

Adenylate cyclase generates the second messenger, cAMP, from ATP. G-protein becomes inactivated by hydrolyzing GTP to GDP. cAMP activates intracellular protein kinases.

Stretching of the uterus during childbirth sends?

Afferent impulses to hypothalamus to stimulate oxytocin release. Infant suckling also stimulates oxytocin release.

Posterior pituitary gland

Antidiuretic hormone (ADH), Oxytocin

Hyposecretion of aldosterone:

As in Addison's disease (deficiency in mineralocorticoids and glucocorticoids) hyperkalemia, Na+ wasting, volume depletion, and hypotension

Hyposecretion of cortisol:

As in Addison's disease (deficiency in mineralocorticoids and glucocorticoids), weight loss, plasma Na+ and glucose levels drop, hyperkalemia, and hypotension.

Hypersecretion of cortisol:

As in Cushing's syndrome, depressed bone and cartilage formation, depressed immune system, inhibits inflammatory mediators, loss of muscle protein, persistently elevated blood sugar, water and salt retention leading to edema and hypertension.

Explain the amplification or "snowballing" effect.

Because each activated adenylate cyclase generates a large amount of cAMP, and a single kinase can phosphorylate many proteins, a single hormone binding to a receptor can generate millions of final product proteins. This is what is meant by the amplification effect.

polyphagia

Because insulin is unavailable to allow the body to utilize glucose, patient feels hungry

Cortisol regulation:

CRH from hypothalamus stimulates ACTH from anterior pituitary. ACTH stimulates cortisol release. Stress (physical or emotional) also stimulates cortisol release. Via negative feedback, cortisol inhibits ACTH and CRH release. Cortisol levels follow a diurnal cycle with peak levels in the morning (8:00 AM) and lowest levels around midnight-3:00 AM.

Type I Diabetes Mellitus:

Characterized by absolute insulin deficiency due to destruction of pancreatic beta cells.

Type II Diabetes Mellitus:

Characterized by relative insulin deficiency and insulin resistance.

Skin

Cholecalciferol-precursor to calcitriol, produced by skin upon UV light exposure. Calcitriol allows Ca2+ absorption from diet

Describe the basic anatomy of the pancreas?

Comprised of both endocrine and exocrine cells; acinar cells (exocrine) produce enzymes which are secreted into the small intestine to digest ingested fat, protein, and carbohydrate. Scattered among acinar cells are pancreatic islets (Islets of Langerhans) which contain two major hormone producing cell populations, beta cells and alpha cells.

Describe the Consequences of Thyroid Hormones (TH) hyper-secretion ?

Cretinism in children (mental retardation, short disproportionately sized body, poorly developed sexual characteristics. In adults, called myxedema (low metabolic rate, feel cold, constipation, lethargy, mental sluggishness.

Polydipsia

Dehydration stimulates the thirst response

Hyposecretion of ADH results in?

Diabetes insipidus, a syndrome of intense thirst and huge urine output. Can be caused by insufficient ADH production, or kidney becomes insensitive to ADH.

Define prostaglandins (PGs) and describe their effects.

Eicosanoids derived from arachidonic acid found in cell membranes. Involved in blood clotting, uterine contractions, GI tract motility, and inflammation.

Explain the chemical relationship between epinephrine and neurotransmitters.

Epinephrine is a hormone and a neurotransmitter. Epinephrine, when released by the adrenal gland into the blood, is a hormone. When released by nerve axons to act on other neurons or glands, it is a neurotransmitter. Epinephrine, along with norepinephrine, dopamine, histamine, and seratonin, are monoamine neurotransmitters.

Kidney

Erythropoietin (EPO)-stimulates RBC production in bone marrow Renin-raises blood pressure by initiating RAAS

Describe the consequences of hyper-secretion of PTH

Excessive bone resorption; osteomalacia, osteoporosis; depresses nervous system, weak skeletal muscles; Ca2+ deposits (e.g. kidney stones)

acidosis

Fat is broken down to be used for fuel. Fatty acid metabolites (ketone bodies) from fat breakdown cause

Hyposecretion of GH

In childhood results in pituitary dwarfism (short but with normal body proportions; in adults there is essentially no effect.

Describe the functions of thyroid hormones?

Increases basal metabolic rate and heat production; regulates normal tissue growth and development in skeletal and nervous systems; promotes normal sexual reproductive maturity; promotes glucose catabolism, protein synthesis; enhances effects of SNS

Briefly describe the mechanism of action of insulin.

Insulin injections are primary medications for both types. Type II diabetes can be managed by lifestyle modifications (weight loss, regular exercise, healthy diet). Pharmacological therapies include biguanides, sulfonylureas, and meglitinides.

Discuss the role of calcitonin in calcium regulation.

Lowers serum Ca2+ levels by inhibiting osteoclast activation. Often used to protect bone in diseases like osteoporosis and Paget's disease. Physiologically, doesn't play much a role in Ca2+ regulation; mostly relevant pharmacologically

Pineal gland

Melatonin

Describe the Consequences of Thyroid Hormones (TH) hypo-secretion ?

Most common is Graves' disease (increased heart rate, feel hot, weight loss despite adequate food, sweating, exophthalmy

Aldosterone function:

Most potent mineralocorticoid, aldosterone promotes synthesis of Na+/K+ pump in the kidney; drives Na+ reabsorption and K+ excretion in urine. Water reabsorption follows Na+ back into the blood. Thus, aldosterone acts to raise blood volume and blood pressure.

Cortisol function:

Most significant and prevalent glucocorticoid in humans; promotes gluconeogenesis by catabolizing adipose tissue and proteins to yield fatty acids and amino acids, respectively. Also enhances SNS vasoconstriction and raises blood pressure. Exogenous cortisol is used for its potent anti-inflammatory properties in diseases such as rheumatoid arthritis and asthma.

Skeleton

Osteocalcin-increases insulin production and sensitivity (levels are low in Type II diabetes)

Describe the anatomy of the adrenal glands

Paired adrenal glands are pyramid-shaped and sit atop the kidneys.

Describe the anatomical & physiological relationship between the hypothalamus and pituitary.

Pituitary gland has two lobes, anterior and posterior, situated in the sella turcica of the sphenoid bone. Superior to the pituitary gland is the hypothalamus, which is connected to the pituitary gland via a stalk, the infundibulum.

Hypothalamus

Prolactin inhibiting hormone (PIH), Gonadotropin releasing hormone (GnRH), Thyrotropin releasing hormone (TRH), Growth hormone releasing hormone (GHRH), Grow hormone inhibiting hormone (GHIH), Corticotropin releasing hormone (CRH)

What drugs block PGs?

Prostaglandins are blocked by Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen and COX inhibitors like aspirin.

PTH Effects:

Raises blood Ca2+ levels by:

Describe their regulation?

Regulation: TRH stimulates TSH release, which stimulates TH release; TH inhibits TRH and TSH release via negative feedback. GHIH, high levels of glucocorticoids, and high levels of iodine inhibit TH release.

Aldosterone regulation:

Release stimulated primarily by Ang II and high K+ blood levels. Under stress, ACTH can also stimulate aldosterone release. Increased blood pressure, atrial natriuretic peptide (ANP), and low blood levels of K+ inhibit aldosterone release.

Describe the mechanism of steroid hormone action via intracellular receptors and the activation of gene transcription.

Steroid hormones (and thyroid hormone) are lipid soluble and penetrate the PM to bind to intracellular receptors. The activated hormone-receptor complex binds to DNA in the nucleus and acts as a transcription factor and promotes transcription of a particular gene.

Review and know the role of the adrenal medulla in the "fight or flight" response.

Stressful stimuli (short-term) cause the hypothalamus to stimulate the adrenal medulla via preganglionic neuron, causing primarily epinephrine release into the blood. Result mimics SNS activation (increased heart rate, blood pressure, sweating, bronchodilation, increased blood flow to skeletal muscle, and increased blood glucose).

Hypersecretion of ADH is

Syndrome of Inappropriate ADH secretion (SIADH), caused by certain cancers or neurosurgery. Symptoms are retention of fluid, headache and disorientation due to brain edema, weight gain, and reduced plasma osmolality.

list the hormones from the cortex

The adrenal cortex is glandular tissue composed of three layers. Outermost layer is zona glomerulosa which produces mineralocorticoids (e.g. aldosterone) to regulate mineral and water balance in the blood. The middle layer is the zona fasciculata, which produces primarily glucocorticoids (e.g. cortisol) to maintain blood glucose levels. The inner layer is the zona reticularis, which produces primarily gonadocorticoids (e.g. androstenedione), which contribute to sex drive and axillary and pubic hair development in women. Insignificant effect in males. N.B. The amount of adrenal gonadocorticoids is insignificant compared to that produced by the gonads.

Second messengers, etc

The other major second messenger is Ca2+. Intracellular Ca2+ is released when the effector enzyme phospholipase C cleaves PIP2 to IP3 and Diacylglycerol.

Define releasing hormone and inhibiting hormone.

The posterior pituitary is neural tissue and releases the neurohormones ADH and oxytocin. Oxytocin is primarily synthesized by paraventricular neurons of the hypothalamus; ADH is primarily synthesized by the supraoptic neurons of the hypothalamus. These two neurohormones travel down the axons of the hypothalamic-hypophyseal tract and stored in axon terminals. Hypothalamic neurons synthesize GHRH, GHIH, PIH, GnRH, TRH, CRH. When stimulated, the hypothalamus releases these hormones into the hypophyseal portal system. The hormones travel through the portal blood to stimulate or inhibit release of hormones GH, TSH, ACTH, FSH, LH, PRL from the anterior pituitary gland.

Discuss the importance of the "regulatory circuit" or "axis" between the hypothalamus, pituitary and target organs.

The regulatory circuit entails hypothalamic stimulation of the posterior pituitary (neurally) or anterior pituitary (hormonally) to cause pituitary hormone release. Hormones released from the target organ exert negative feedback on the hypothalamus and pituitary gland to prevent further activation of the system. Exception is oxytocin which operates on a positive feedback system.

Describe the location of the parathyroid glands.

There are typically 4 parathyroid glands, two each on the posterior aspect of the thyroid gland lobes. PTH is produced by parathyroid cells (aka Chief Cells).

Describe the location and microanatomy of the thyroid gland.

Thyroid gland is located in the anterior neck, inferior to larynx. Bilateral lobes are connected by the isthmus. Gland is composed of hollow follicles surrounded by epithelial cells called follicular cells. Follicular cells produce thyroglobulin. Follicles contain colloid, a matrix in which iodine is attached to thyroglobulin. Thyroid hormone is derived from this iodinated thyroglobulin. Embedded within the follicle epithelium are parafollicular cells, which produce calcitonin.

Describe the functions of thyroid hormones, their regulation and the consequences of hyper- and hyposecretion.

Thyroid hormones (thyroxine or T4 and triiodothyronine or T3)

Regardless of type diabetes

both are characterized by polyuria, polydipsia, and polyphagia. High concentration of glucose in blood draws water out in urine

Alcohol inhibits ADH release

causing dehydration

Polyuria

dehydration, and decreased blood volume

Endocrine system

egulates reproduction, growth&development, water, electrolyte & nutrient balance, cellular metabolism, and mobilization of body defenses via chemical messengers (hormones) that bind to cellular receptors on target organs, inducing a response with a delay (seconds to days) that is long-lived

Adrenal gland

epinephrine, norepinephrine, mineralocorticoids, glucocorticoids, gonadocorticoids

GI Tract:

gastrin-stimulates smooth muscle of stomach and HCl production secretin-stimulate bile production and bicarbonate-rich juice from pancreas CCK-stimulates bile ejection from gall bladder and enzyme-rich juice from pancreas

Anterior pituitary gland

growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), ACTH (adrenocorticotropic hormone), follicle-stimulating hormone (FSH), luteinizing hormone (LH)

Pancreas

insulin, glucagon, somatostatin

list the hormones from the medulla

is nervous tissue, a modified postganglionic neuron of the SNS. Medullary chromaffin cells synthesize and release the catecholamines, epinephrine (80%) and norepinephrine (20%). Catecholamines mimic SNS activation, causing increased HR, blood pressure, vasoconstriction, bronchodilation, increased blood sugar, and sweating

Adipose tissue:

leptin-"satiety hormone", stimulates energy expenditure resistin- insulin antagonist adiponectin- enhances sensitivity to insulin

Positive feedback:

less common mechanism of homeostatic control in which output from the system accelerates or intensifies the original stimulus

Endocrine

long-distance chemical signals (e.g. insulin released from pancreas allows fat and muscle cells throughout the body to take up glucose)

Describe the consequences of hypo-secretion of PTH

low blood Ca2+ and hyperexcitability of neurons and muscle; twitching and convulsions

Negative feedback:

mechanism of homeostatic control in which output from the system shuts off or reduces the intensity of the original stimulus

Parathyroid gland

parathyroid hormone (PTH)

(ADH) Oxytocin Antidiuretic Hormone

prevents loss of water to the urine in the kidney by allowing water reabsorption back into the blood

Alpha cells

produce glucagon which raises blood sugar by stimulating the liver to break down glycogen, release glucose to the blood, and synthesize more glucose (gluconeogenesis).

Beta cells

produce insulin which lowers blood sugar by allowing muscle and fat to take up glucose, inhibiting glycogenolysis, and inhibits conversion of amino acids and fats to glucose. Insulin also stimulates ATP production, protein synthesis, glycogen formation, and conversion of glucose to fat in adipose tissue.

Nervous system

regulates muscles and glands via electrochemical impulses delivered by neurons, inducing a rapid response (within milliseconds) that is short-lived

Discuss the role of PTH regulation?

released in response to hypocalcemia; inhibited by hypercalcemia.

Osmoreceptors in the hypothalamus

respond to increased solute concentration in body fluid by stimulating ADH release.

Paracrine

short-distance chemicals that exert effect on nearby cells; that is, within the same tissue, but not the same cells that released them (ex. somatostatin released by delta cells of the pancreas inhibits insulin release from pancreatic beta cells).

Autocrine

short-distance chemicals that exert effects on cells that secrete them (e.g. prostaglandins released from smooth muscle cells cause those smooth muscle cells to contract).

Oxytocin

stimulates uterine contractions to initiate labor and produces milk "letdown" reflex (milk ejection from mammary gland). Both are examples of positive feedback mechanisms.

Gonads

testosterone and estrogen

Thymus

thymulin, thymopoietins, thymosin-involved in normal development of T lymphocytes

Thyroid gland

thyroid hormone (TH) and calcitonin