Endocrine 2

growth hormone (GH) (also called somatotropin)

growth hormone (GH) (also called somatotropin)

produced by somatotropic cells, has direct actions on metabolism and indirect growth-promoting actions

direct actions of growth hormone on metabolism

glucose-sparing actions decrease rate of cellular glucose uptake and metabolism (anti-insulin effects), triggers liver to break down glycogen into glucose, increases blood levels of fatty acids for use as fuel and encourages cellular protein synthesis

indirect actions from growth hormone

triggers liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs), IGFs stimulate cellular uptake of nutrients used to synthesize DNA and proteins needed for cell division and formation of collagen and deposition of bone matrix, stimulates most cells to enlarge and divide (major targets are bone and skeletal muscle)

growth hormone regulation of secretion

growth hormone release or inhibition regulated by hypothalamic hormones on somatotropic cells (growth hormone-releasing hormone and growth hormone-inhibiting hormone)

growth hormone-releasing hormone (GHRH)

stimulates GH release, triggered by low blood GH or glucose, or high amino acid levels

growth hormone-inhibiting hormone (GHIH)

inhibits release of GH, triggered by increase in GH and IGF levels

hypersecretion of GH

typically caused by anterior pituitary tumor, results in gigantism in children and acromegaly (overgrowth of hands, feet, and face) in adults

hyposecretion of GH

pituitary dwarfism in children and usually no problems in adults

thyroid-stimulating hormone (TSH) (also called thyrotropin)

tropic hormone, produced by thyrotropic cells, stimulates normal development and secretory activity of thyroid, release is triggered by thyrotropin-releasing hormone (TRH) from hypothalamus, inhibited by rising blood levels of thyroid hormones that act on both pituitary and hypothalamus, too much thyroid hormone can act as a negative feedback

adrenocorticotropic hormone (ACTH) (also called corticotropin)

secreted by corticotropic cells, stimulates adrenal cortex to release corticosteroids

regulation of ACTH release

triggered by corticotropin-releasing hormone (CRH) from hypothalamus in daily rhythm with highest levels in the morning, fever/hypoglycemia/stressors can alter release of CRH

gonadotropins (FSH and LH)

follicle-stimulating hormone and luteinizing hormone are secreted by gonadotropic cells, FSH stimulates production of games (egg or sperm), LH promotes production of gonadal hormones, both are absent from blood in prepubertal boys and girls

regulation of gonadotropin release

triggered by gonadotropin-release hormone (GnRH) during and after puberty, suppressed by gonadal hormones

Prolactin (PRL)

secreted by prolactin cells, stimulates milk production in females, regulation primarily controlled by prolactin-inhibiting hormone (PIH)(also called dopamine), PIH prevents release of PRL until needed with the decreased levels leading to lactation, increased estrogen stimulate PRL, suckling stimulates PRL release and promotes continued milk production (positive feedback mechanism)

hypersecretion of prolactin

more common than hyposecretion, most frequent abnormality of anterior pituitary tumors, inappropriate lactation (galactorrhea), lack of menses, infertility in females, impotence in males

thyroid gland

butterfly-shaped gland in anterior neck on the trachea, consists of isthmus, follicles, colloid, parafollicular cells

isthmus

median mass connecting two lateral lobes

follicles

hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin

colloid

fluid of follicle lumen containing thyroglobulin plus iodine and is precursor to thyroid hormone

parafollicular cells

produce hormone calcitonin

thyroid hormone

body’s major metabolic hormone, found as T4 (thyroxine) and T3 (triiodothyronine), affects virtually every cell in the body, enters cells and binds to intracellular receptors within nucleus

T4 (thyroxine)

major form that consists of two tyrosine molecules with four bound iodine atoms

T3 (triiodothyronine)

form that has two tyrosines with three bound iodine atoms, must be converted to T4 at tissue level

effects of thyroid hormone

increases basal metabolic rate and heat production (calorigenic effect), regulates tissue growth and development (critical for normal skeletal and nervous system development), maintains blood pressure (increases adrenergic receptors in blood vessels)

hypthalamic-pituitary-thyroid axis

TRH secreted by hypothalamus to stimulate the release of TSH from anterior pituitary cells, TSH binds to receptors on epithelial cells in thyroid gland which stimulates that gland to synthesize and release thyroid hormones T3 and T4

thyroid hormone synthesis

1. thyroglobulin synthesized and discharged into follicle lumen

2. iodide is trapped

3. iodide oxidized → converts to iodine

4. iodine is attached to tyrosine forming monoiodotyrosine (MIT) if only one iodine attaches or diiodotyrosine (DIT) if two iodines attach

5. iodinated tyrosines link to form T3 (if MIT and DIT link) and T4 (if two DITs link)

6. colloid is endocytosed by follicular cells, vesicle is then combined with a lysosome

7. lysosomal enzymes cleave T3 and T4 from thyroglobulin (mostly T4 is secreted into blood stream but T3 is also secreted)

transport and regulation of thyroid hormone

T4 and T3 transported by thyroxine-binding globulins (TBGs), T3 is is 10 times more active than T4 but both bind to target receptors, TH release is regulated by negative feedback

hyposecretion of TH

can lead to myxedema in adults, symptoms includes low metabolic rate/thick and dry skin/puffy eyes/feeling chilled/constipation/edema, a goiter may develop which can lead to an enlarged thyroid

Graves disease

hypersecretion of TH, autoimmune disease that the body makes abnormal antibodies that mimic TSH stimulating TH release, symptoms include elevated metabolic rate/sweating/rapid and irregular heartbeats/nervousness

calcitonin

produced by parafollicular (C) cells in response to high calcium levels, antagonist to parathyroid hormone (PTH), at higher than normal doses can inhibit osteoclast activity and prevent release of calcium from bone matrix and can stimulate calcium uptake and incorporation into bone matrix

parathyroid gland

4-8 tiny yellow-brown glands embedded in posterior aspect of thyroid, contains oxyphil cells and parathyroid cells that secrete parathyroid hormone (PTH) which is most important hormone in calcium homeostasis, target organs are skeleton/kidneys/intestines

parathyroid gland functions

in response to low calcium levels, stimulate osteoclasts to digest bone matrix and release calcium to blood, enhances reabsorption of calcium and secretion of phosphate by kidneys, promotes activation of vitamin D by kidneys which leads to increased absorption of calcium by intestinal mucosa

hyperparathyroidism

due to parathyroid gland tumor, calcium leaches from bones causing softening and deformation, elevated calcium depresses nervous system and may contribute to formation of kidney stones

osteitis fibrosa cystica

severe skeletal disorder resulting in easily fractured bones

hypothyroidism

following gland trauma or removal can cause hypocalcemia resulting in tetany/respiratory paralysis/death

adrenal gland (suprarenal glands)

paired/pyramid-shaped organs atop kidneys, two glands in one, produces over 24 different hormones called corticosteroids

adrenal cortex

three layers of glandular tissue that synthesize and secrete several different hormones

adrenal medulla

nervous tissue that is a part of sympathetic nervous system

3 layers of cortical cells of adrenal cortex

zona glomerulosa, zona fasciculata, zona reticularis

mineralocorticoids (salt)

zona glomerulosa, regulate electrolyte concentrations in ECF, sodium affects ECF volume/blood volume/blood pressure/levels of other ions, potassium sets resting membrane potential of cells

aldosterone

most potent mineralocorticoid, stimulates sodium reabsorption by kidneys, stimulates potassium elimination by kidneys, effects are short lived, stimulates synthesis and activation of sodium/potassium ATPase transport pumps

factors that regulate aldosterone secretion

renin-angiotensin-aldosterone mechanism, plasma concentration of potassium, ACTH, atrial natriuretic peptide

Renin-angiotensin-aldosterone mechanism

decreased blood pressure stimulates special cells in kidneys, these cells release renin into blood, renin cleaves off angiotensinogen that triggers and enzyme cascade resulting in conversion in angiotensin II (a potent stimulator of aldosterone release - zona glomerulosa)

plasma concentration of potassium

increased potassium directly influences zona glomerulosa cells to release aldosterone, low levels inhibit it

ACTH

can cause small increases of aldosterone during periods of increased stress

atrial natriuretic peptide (ANP)

inhibitory, secreted by heart in response to high blood pressure, blocks renin and aldosterone secretion to decrease blood pressure, won’t produce angiotensin (II)

glucocorticoids (sugar)

zona fasciculata, influence metabolism of most cells and help us resist stressors, keep blood glucose levels relatively constant, maintain blood pressure by increasing action of vasoconstrictors, include cortisol(hydrocortisone)/cortisone/corticosterone

regulation of glucocorticoids secretion

cortisol is released in response to ACTH (released in response to CRH which is released in response to low cortisol levels), cortisol secretion cycles are governed by patterns of eating and activity, acute stress interrupts cortisol rhythm, CNS can override cortisol inhibition of ACTH and CRH leading to more cortisol secretion

glucocorticoid action

cortisol causes increase in blood levels of glucose/fatty acids/amino acids, prime metabolic effect is gluconeogenesis (formation of glucose from fats and proteins), enhance vasoconstriction

excessive levels of glucocorticoids

depress cartilage and bone formation, inhibit inflammation by decreasing release of inflammatory chemicals, depress immune system, disrupt normal cardiovascular/neural/gastrointestinal functions

Cushing’s syndrome/disease

hypersecretion of glucocorticoids, depresses cartilage/bone formation and immune system, inhibits inflammation, disrupts neural/cardiovascular/gastrointestinal function, caused by tumor on pituitary/lungs/pancreas/kidney/adrenal cortex, signs of “moon face” and “buffalo hump”

Addison’s disease

hyposecretion of glucocorticoids, usually involves both deficits in both glucocorticoids and mineralcorticoids, decrease in plasma glucose and sodium levels, weight loss, severe dehydration, hypotension, characteristic bronzing of skin due to high levels of ACTH which triggers melanin production in melanocytes

gonadocorticoids (adrenal sex hormone)

zona reticularis, weak androgens are converted to testosterone in tissue cells with some to estrogen, contributes to onset of puberty and appearance of secondary sex characteristics, sex drive in women, and source of estrogens in postmenopausal women

Adrenogenital syndrome

hypersecretion of gonadocorticoids, not noticeable in adult males, females get a beard, masculine pattern of body hair, prepubertal boys have their reproductive organs mature and secondary sex characteristics emerge early

medullary chromaffin cells

modified postganglionic sympathetic neurons, synthesize catcholamines (epinephrine and norepinephrine 80%-20%)

catecholamines effects

vasoconstriction, increased heart rate, increased blood glucose levels, blood diverted to brain/heart/skeletal muscle, epinephrine is more of a stimulator of metabolic activities, norepinephrine had more of an influence on peripheral vasoconstriction and blood pressure

short term stress

hypothalamus activates the adrenal medulla via neural stimuli

long term stress

the hypothalamus activates the adrenal cortex via hormonal stimuli, greatly reinforces the continuing short term response

hypersecretion of epinephrine

leads to symptoms of uncontrolled sympathetic nervous system (hyperglycemia, increased metabolic rate, rapid heartbeat, palpitations, etc.), can be due to pheochromocytoma (tumor of medullary chromaffin cells)