Endocrine System

goiter

* goiter = enlarged thyroid gland However, TSH does more than just stimulate T3 and T4 production. TSH also increases protein synthesis in follicular epithelial cells, increases DNA replication and cell division, and increases the amount of rough endoplasmic reticulum and other cellular machinery required by follicular epithelial cells for protein synthesis. Therefore, if thyroid cells are exposed to greater TSH concentrations than normal, they will undergo hypertrophy; that is, they will increase in size.

differences between anterior and posterior pituitary hormone secretion

- First, the axons of the hypothalamic neurons that secrete the posterior pituitary hormones leave the hypothalamus and end in the posterior pituitary, whereas those that secrete the hypophysiotropic hormones remain in the hypothalamus, ending on capillaries in the median eminence. - Second, most of the capillaries into which the posterior pituitary hormones are secreted immediately drain into the general circulation, which carries the hormones to the heart for distribution to the entire body. In contrast, the hypophysiotropic hormones enter capillaries in the median eminence of the hypothalamus that do not directly join the main bloodstream but empty into the hypothalamo-hypophyseal portal vessels, which carry them to the cells of the anterior pituitary gland. - When an anterior pituitary gland hormone is secreted, it will diffuse into the same capillaries that delivered the hypophysiotropic hormone. These capillaries then drain into veins, which enter the general blood circulation, from which the anterior pituitary gland hormones come into contact with their target cells.

actions of thyroid hormone

- T3 stimulates carbohydrate absorption from the small intestine and increases fatty acid release from adipocytes. These actions provide energy that helps maintain metabolism at a high rate. Much of that energy is used to support the activity of Na+/K+-ATPases throughout the body; these enzymes are stimulated by T3. - T3 up-regulates beta-adrenergic receptors in many tissues, notably the heart and nervous system. It should not be surprising, therefore, that the symptoms of excess thyroid hormone concentration closely resemble some of the symptoms of excess epinephrine and norepinephrine (sympathetic nervous system activity). - T3 is required for normal production of growth hormone from the anterior pituitary gland.

vasopressin (aka ADH) function

- acts on smooth muscle cells around blood vessels to cause their contraction, which constricts the blood vessels and thereby increases blood pressure. - also acts within the kidneys to decrease water excretion in the urine, thereby retaining fluid in the body and helping to maintain blood volume. - because of its kidney function, vasopressin is also known as antidiuretic hormone (ADH)

congentital hypothyroidism

- caused by absence of T3 - This syndrome is characterized by a poorly developed nervous system and severely compromised intellectual function (mental retardation). In the United States, the most common cause is the failure of the thyroid gland to develop normally.

Hashimoto's disease

- cells of the immune system attack thyroid tissue - leads to hypothyroidism

Graves' disease

- characterized by the production of antibodies that bind to and activate the TSH receptors on thyroid gland cells, leading to chronic overstimulation of the growth and activity of the thyroid gland - leads to hyperthyroidism - Hyperthyroidism can be very serious, particularly because of its effects on the cardiovascular system (largely secondary to its permissive actions on catecholamines).

cortisol and growth

- high levels inhibit bone growth - also breaks down bone and inhibits the secretion of growth hormone and IGF-1

growth hormone (GH)

- secreted by the anterior pituitary gland, has little effect on fetal growth but is the most important hormone for growth after the age of 1-2 years - stimulation of cell division in its many target tissues - Thus, growth hormone promotes bone lengthening by stimulating cell division of the chondrocytes in the epiphyseal plates, thereby continuously widening the plates and providing more cartilaginous material for bone formation - acts indirectly via mitogenic hormone IGF-1, whose synthesis and release by the liver are induced by growth hormone - growth hormone directly stimulates protein synthesis in various tissues and organs, particularly muscle - also stimulates gluconeogenesis in the liver

causes of hyporesponsiveness:

1. can result from deficiency or loss of function of receptors for the hormone. 2. the receptors for a hormone may be normal but some signaling event that occurs within the cell after the hormone binds to its receptors may be defective. For example, the activated receptor may be unable to stimulate formation of cyclic AMP or another component of the signaling pathway for that hormone. 3. A third cause of hyporesponsiveness applies to hormones that require metabolic activation by some other tissue after secretion. There may be a deficiency of the enzymes that catalyze the activation. For example, some men secrete testosterone (the major circulating androgen) normally and have normal receptors for androgens. However, these men are missing the intracellular enzyme that converts testosterone to dihydrotestosterone, a potent metabolite of testosterone that binds to androgen receptors and mediates some of the actions of testosterone on secondary sex characteristics such as the growth of facial and body hair.

list the six hormones secreted by the anterior pituitary gland:

1. follicle-stimulating hormone (FSH) 2. luteinizing hormone (LH) 3. growth hormone (GH, also known as somatotropin) 4. thyroid-stimulating hormone (TSH, also known as thyrotropin) 5. prolactin 6. adrenocorticotropic hormone (ACTH, also known as corticotropin) * Each of the last four is secreted by a distinct cell type in the anterior pituitary gland, whereas FSH and LH, collectively termed gonadotropic hormones (or gonadotropins) because they stimulate the gonads, are often secreted by the same cells.

The adrenal cortex is composed of ___ distinct layers. List them.

3 zona glomerulosa zona fasciculata zona reticularis

parathyroid hormone

A decrease in the plasma Ca2+ concentration directly stimulates PTH secretion. PTH then exerts several actions on bone and other tissue that increase calcium release into the blood, thereby restoring plasma Ca2+ to normal.

tropic hormones

A hormone that stimulates the secretion of another hormone is often referred to as a tropic hormone. The tropic hormones usually stimulate not only secretion but also the growth of the stimulated gland.

primary hyposecretion

An endocrine gland may be secreting too little hormone because the gland is not functioning normally, a condition termed primary hyposecretion. Examples include (1) partial destruction of a gland, leading to decreased hormone secretion; (2) an enzyme deficiency resulting in decreased synthesis of the hormone; and (3) dietary deficiency of iodine, specifically leading to decreased secretion of thyroid hormones. Many other causes, such as infections and exposure to toxic chemicals, have the common denominator of damaging the endocrine gland or reducing its ability to synthesize or secrete the hormone.

major steroid hormones secreted by adrenal cortex

Dehydroepiandrosterone (DHEA) and androstenedione are androgens—that is, testosterone-like hormones. Cortisol and corticosterone are glucocorticoids, and aldosterone is a mineralocorticoid that is only produced by one part of the adrenal cortex. **All of the steroid hormones are derived from cholesterol, which is either taken up from the extracellular fluid by the cells or synthesized by intracellular enzymes.

dopamine

Dopamine is released by hypothalamus into a special circulatory system called a portal system, which carries the hormone to the pituitary gland; there, it acts to inhibit the activity of certain endocrine cells.

down-regulation

Down-regulation is a decrease in receptor number, often from exposure to high concentrations of the hormone. This temporarily decreases target-cell responsiveness to the hormone, thereby preventing overstimulation.

hormones of the gonads

Endocrine cells in both the testes and the ovaries do not express the enzymes required to produce aldosterone and cortisol. They possess high concentrations of enzymes in the androgen pathways leading to androstenedione, as in the adrenal cortex.

progesterone

Endocrine cells of the corpus luteum, an ovarian structure that arises following each ovulation, secrete progesterone. This steroid is critically important for maintaining a pregnancy. Progesterone is also synthesized in other parts of the body—notably, the placenta in pregnant women and the adrenal cortex in both males and females.

cortisol

In addition to its effects on organic metabolism, cortisol exerts many other effects, including facilitation of the body's responses to stress and regulation of the immune system

Enzymatic breakdown of hormones

In addition, enzymes in the blood and tissues rapidly break down catecholamine and peptide hormones. These hormones therefore tend to remain in the bloodstream for only brief periods—minutes to an hour. In contrast, protein-bound hormones are protected from excretion or metabolism by enzymes as long as they remain bound. Therefore, removal of the circulating steroid and thyroid hormones generally takes longer, often several hours to days.

synthesis of steroid hormones

In both the gonads and the adrenal cortex, the hormone-producing cells are stimulated by the binding of an anterior pituitary gland hormone to its plasma membrane receptor. These receptors are linked to Gs proteins, which activate adenylyl cyclase and cAMP production. The subsequent activation of protein kinase A by cAMP results in phosphorylation of numerous intracellular proteins, which facilitate the subsequent steps in the process.

Composition of pituitary gland

In humans, the pituitary gland is primarily composed of two adjacent lobes called the anterior lobe—usually referred to as the anterior pituitary gland—and the posterior lobe—usually called the posterior pituitary. * The posterior pituitary is not actually a gland but, rather, an extension of the neural components of the hypothalamus.

zona fasciculata/zona reticularis

In humans, the zona fasciculata primarily produces cortisol and the zona reticularis primarily produces androgens, but both zones produce both types of steroid.

hypothyroidism

In iodine deficiency, the synthesis of thyroid hormone is compromised, leading to a decrease in the plasma concentration of this hormone. This, in turn, releases the hypothalamus and anterior pituitary gland from negative feedback inhibition. This leads to an increase in TRH concentration in the portal circulation that drains into the anterior pituitary gland. Plasma TSH concentration is increased due to the increased TRH and loss of thyroid hormone negative feedback on the anterior pituitary gland. The resulting overstimulation of the thyroid gland can produce goiters that can achieve astounding sizes if untreated

up-regulation

In the context of hormones, up-regulation is an increase in the number of a hormone's receptors in a cell, often resulting from a prolonged exposure to a low concentration of the hormone. This has the effect of increasing target-cell responsiveness to the hormone.

insulin and growth

Insulin stimulates storage of fat and inhibits protein degradation. Thus, it is not surprising that adequate amounts of insulin are necessary for normal growth.

Aldosterone synthesis

Production of aldosterone is under the control of another hormone called angiotensin II, which binds to plasma membrane receptors in the adrenal cortex to activate the inositol trisphosphate second-messenger pathway. This is different from the more common cAMP-mediated mechanism by which most steroid hormones are produced, as previously described. Once synthesized, aldosterone enters the circulation and acts on cells of the kidneys to stimulate Na+ and H2O retention, and K+ and H+ excretion in the urine.

steps in steroid secretion

Steroid hormones diffuse (because hydrophobic) across the plasma membrane into circulation. Because of their lipid nature, steroid hormones are not highly soluble in blood. Consequently, the majority of steroid hormones are reversibly bound in plasma to carrier proteins such as albumin and various other specific proteins.

congenital adrenal hyperplasia (CAH)

The absence of an enzyme required for the formation of cortisol by the adrenal cortex can result in the shunting of the cortisol precursors into the androgen pathway. Excess adrenal androgen production results in virilization of the genitalia of female fetuses; at birth, it may not be obvious whether the baby is phenotypically male or female.

amine hormones

The amine hormones are derivatives of the amino acid tyrosine. They include thyroxine and triiodothyronine (thyroid hormones), and norepinephrine, epinephrine, and dopamine (catecholamines). Norep/epi = produced by the adrenal medulla. Dopamine = produced by the hypothalamus.

zona glomerulosa

The cells of the outer layer—the zona glomerulosa—express the enzymes required to synthesize corticosterone and then convert it to aldosterone but do not express the genes that code for the enzymes required for the formation of cortisol and androgens. Therefore, this layer synthesizes and secretes aldosterone but not the other major adrenocortical hormones.

hypophysiotropic hormones

The collection of hypothalamic hormones that regulate anterior pituitary gland function

hypothalamo-hypophyseal portal vessels (or portal veins)

The hypothalamo-hypophyseal portal vessels pass down the infundibulum and enter the anterior pituitary gland, where they drain into a second set of capillaries, the anterior pituitary gland capillaries. Thus, the hypothalamo-hypophyseal portal vessels offer a local route for blood to be delivered directly from the median eminence to the cells of the anterior pituitary gland. As we will see shortly, this local blood system provides a mechanism for hormones synthesized in cell bodies in the hypothalamus to directly alter the activity of the cells of the anterior pituitary gland, bypassing the general circulation and thus efficiently and specifically regulating hormone release from that gland.

Hormone elimination occurs in...

The liver and the kidneys are the major organs that metabolize or excrete hormones. But sometimes a hormone is metabolized by the cells upon which it acts. In the case of some peptide hormones, for example, endocytosis of hormone-receptor complexes on plasma membranes enables cells to remove the hormones rapidly from their surfaces and catabolize them intracellularly.

sex steroids and growth

The major growth-promoting effect of the sex steroids is to stimulate the secretion of growth hormone and IGF-1. Unlike growth hormone, however, the sex steroids not only stimulate bone growth but ultimately stop it by inducing epiphyseal closure.

pendrin

The negatively charged iodide ions diffuse to the apical membrane of the follicular epithelial cells and are transported into the colloid by an integral membrane protein called pendrin (step 2). Pendrin is a sodium-independent chloride/iodide transporter.

secondary hyposecretion

The other major cause of hyposecretion is secondary hyposecretion. In this case, the endocrine gland is not damaged (at least at first) but is receiving too little stimulation by its tropic hormone. This might occur, for example, if the trophic hormone was being synthesized and released at an abnormally low rate. In the long term, lack of the trophic action of the tropic hormones invariably leads to atrophy of the target gland that can be reversed if the concentration of the trophic hormone in the blood returns to normal.

importance of portal circulatory system in pituitary

The portal circulatory system ensures that hypophysiotropic hormones can reach the cells of the anterior pituitary gland with very little delay.

thyroid hormones

The two thyroid hormones differ by only one iodine atom, a difference noted in the abbreviations T3 and T4. T4 is the primary secretory product of the thyroid gland, but is activated to the much more potent T3 in target tissue.

adrenal gland

There are two adrenal glands, one above each kidney. Each adrenal gland is composed of an inner adrenal medulla, which secretes catecholamines, and a surrounding adrenal cortex, which secretes steroid hormones. The adrenal medulla is really a modified sympathetic ganglion whose cell bodies do not have axons. Instead, they release their secretions into the blood, thereby fulfilling a criterion for an endocrine gland.

thyroid hormones and growth

Thyroid hormone is essential for normal growth because it facilitates the synthesis of growth hormone. T3 also has direct actions on bone, where it stimulates chondrocyte differentiation, growth of new blood vessels in developing bone, and responsiveness of bone cells to other growth factors such as fibroblast growth factor.

rickets

Vitamin D deficiency in children; causes bone deformity

Calcitonin

a hormone that is produced in humans by the parafollicular cells (commonly known as C-cells) of the thyroid gland. Calcitonin is involved in helping to regulate levels of calcium and phosphate in the blood, opposing the action of parathyroid hormone.

Osteoblasts

bone forming cells

osteoclasts

break down bone

iodide trapping

circulating iodide is actively cotransported with sodium ions across the basolateral membranes of the epithelial cells in thyroid

osteomalacia

disease marked by softening of the bone caused by calcium and vitamin D deficiency; in adults

secondary hypersecretion

excessive stimulation of the gland by its tropic hormone

in the thyroid gland, _____ cells secrete thyroxine and _____ cells secrete calcitonin

follicular; parafollicular

hormones most important to human growth

growth hormone, insulin-like growth factors 1 and 2, T3, insulin, testosterone, and estradiol

median eminence

junction of the hypothalamus and infundibulum

high levels of calcium in the blood cause the kidneys to reabsorb ______ (more/less) calcium

less

Osteocytes

mature bone cells

__________stimulates 1-hydroxylase activity in the _________, which produces the active form of vitamin D

parathyroid hormone; kidney

permissiveness

permissiveness means that hormone A must be present in order for hormone B to exert its full effect. - may be due to A's ability to up-regulate B's receptors. For example, epinephrine stimulates the release of fatty acids into the blood from adipocytes, an important function in times of increased energy requirements. However, epinephrine cannot do this effectively in the absence of permissive amounts of thyroid hormones. (thyroid hormones stimulate the synthesis of beta-adrenergic receptors for epinephrine in adipose tissue; as a result, the tissue becomes much more sensitive to epinephrine) However, receptor up-regulation does not explain all cases of permissiveness. Sometimes, the effect may be due to changes in the signaling pathway that mediates the actions of a given hormone.

infundibulum

pituitary stalk, containing axons from neurons in the hypothalamus and small blood vessels; connects pituitary gland to hypothalamus

steroid hormones

ringlike structure; Steroid hormones are primarily produced by the adrenal cortex and the gonads (testes and ovaries), as well as by the placenta during pregnancy. In addition, vitamin D is enzymatically converted in the body to an active steroid hormone.

hyporesponsiveness (definition & example)

target cells do not respond normally to the hormone; hormone resistance ex: type 2 diabetes mellitus, in which the target cells of the hormone insulin are hyporesponsive to this hormone.

primary hypersecretion

the gland is secreting too much of the hormone on its own

Name the two posterior pituitary hormones

the peptides oxytocin and vasopressin

Estradiol

the predominant estrogen present during a woman's lifetime. The ovarian endocrine cells express large amounts of the enzyme aromatase, which catalyzes the conversion of androgens to estrogens

hyperresponsivenss (example)

thyroid hormone causes an up-regulation of beta-adrenergic receptors for epinephrine; therefore, hypersecretion of thyroid hormone causes, in turn, a hyperresponsiveness of target cells to epinephrine. One result of this is the increased heart rate typical of people with increased plasma concentrations of thyroid hormone.

oxytocin function

uterine contractions and milk ejection; bond-pairing