MD1010 - ENDO: Hormones of the Endocrine System

1,25 dihydroxycholecalciferol (1,25DHCC)

endocrine gland - kidney;

class - sterol hormone, with similarities in origin with steroid hormones;

site of production - renal tissues where 1, alpha hydroxylase acts;

biosynthesis - 7-dehydrocholesterol to cholecalciferol, converted to (hormone), involving three tissues, skin, liver, kidney, 1, alpha hydroxylase catalyses the final conversion;

factors affecting release - higher plasma calcium leads to decreased PTH secretion, leading to decreased formation of (hormone);

travels in blood - bound form to vitamin-d binding protein;

site of action - intestine, bone, and kidney;

mechanism of action - enters the cell and binds to receptors;

major actions - increases plasma ionised calcium, increases intestinal calcium absorption, increases phosphate absorption, increases PTH action in the bones, decreases renal calcium excretion, decreases urinary excretion of phosphate Vit D receptors on osteoblasts;

regulation of secretion - blood calcium and plasma PTH levels regulated (hormone);

clinical significance - (hormone) deficiency leads to rickets in children and osteomalacia in adults

adrenocorticotropic hormone (ACTH)

endocrine gland - anterior pituitary as well as ectopic sources such as lung or pancreas;

class - peptide hormone;

site of production - corticotrophs of anterior pituitary;

biosynthesis - protein biosynthesis where large precursor peptide POMC produces (hormone) and beta-LPH;

factors affecting release - increased release caused by stress and AVP, decreased released caused by cortisol, has a diurnal rhythm of release with peak secretion in the early morning;

travels in blood - free form with no binding protein;

site of action - all three layers of the adrenal cortex, acts as a major regulator of cortisol and adrenal androgen release;

mechanism of action - acts on membrane receptors, MC2R, with cAMP as a second messenger;

major actions - increased synthesis of and secretion of cortisol and adrenal androgens, promotes conversion of cholesterol to pregnenolone and stimulates aldosterone biosynthesis although to a lesser extent;

regulation of secretion - negative feedback mechanism, CRH increases (hormone) secretion, which increases cortisol, which inhibits both CRH and (hormone);

clinical significance - ectopic Cushing’s syndrome, pituitary Cushing’s syndrome, hyperpigmentation when (hormone) is in excess in Addison’s disease and pituitary Cushing’s syndrome

antidiuretic hormone (ADH) or arginine vasopressin (AVP)

endocrine gland - posterior pituitary;

class - peptide, nanopeptide;

site of production - synthesised in the supraoptic and paraventricular nuclei in hypothalamus, but released from posterior pituitary;

biosynthesis - protein biosynthesis, prepro to prohormone and active (hormone), stored in vesicles in axon terminals

factors affecting release - increased secretion caused by increased osmolarity, decreased ECF volume, Angiotensin II, pain, and stress, decreased secretion caused by decreased osmolarity, alcohol, and atrial natriuretic peptide

travels in blood - free form, no binding protein

site of action - nephron collecting duct of the kidney, and blood vessels

mechanism of action - acts on membrane receptors, V2 receptor in the kidney activates cAMP, V1a receptor in blood vessels

major actions - increased water reabsorption in collecting ducts by inserting aquaporin 2 water channels, and increases blood vessel constriction

regulation of secretion - stimulated by the osmosensitive neurons causing a release of (hormone) into the posterior pituitary, water ingestion suppresses osmoreceptor firing to shut off (hormone) release, change in blood pressure stimulates or inhibits atrial receptors to regulate (hormone)

clinical significance - deficiency causes cranial diabetes insipidus, renal resistance to (hormone) causes nephrogenic diabetes insipidus, diabetes insipidus causes polyuria and polydipsia, SIADH causes too much (hormone) secretion and low plasma osmolarity and dilutional hyponatraemia

adrenal sex steroids

endocrine gland - adrenal gland;

class - steroid hormones;

site of production - adrenal cortex: zona reticularis;

biosynthesis - steroid hormone synthesis; androstenedione and dehydroepiandrosterone (DHEA) are the major steroids;

factors affecting release - ACTH stimulate the release of (hormone);

travels in blood - bound form: plasma binding proteins

site of action - peripheral tissues

mechanism of action - cross the membrane and bind to cytosolic receptor

major actions - play only a minor role in males, major (hormone) in females: responsible for the development of pubic and axillary hair and for libido

regulation of secretion - hypothalamic-pituitary-adrenal cortical axis: ACTH increases secretion

clinical significance - produce appreciable masculinisation when secreted in excessive amounts: adrenogenital syndrome where there is an increased synthesis of (hormone), leading to masculinisation in females, early development of pubic and axillary hair, and suppression of gonadal function in males and females: congenital adrenal hyperplasia, due to specific enzymatic defects in the synthesis of cortisol leading to hypersecretion of (hormone)

aldosterone

endocrine gland - adrenal gland;

class - steroid hormone;

site of production - adrenal cortex, zona glomerulosa as (hormone) synthase enzyme is present in this zone;

biosynthesis - steroid biosynthesis, from cholesterol to pregnenolone and through (hormone) biosynthesis pathway: very little storage of hormones as they synthesised on demand;

factors affecting release - angiotensin II, increased potassium stimulate (hormone) secretion: increased serum sodium, increased atrial natriuretic peptide hormone decreases (hormone) secretion;

travels in blood - bound form, (hormone) binding protein;

site of action - kidney: late distal tubules and collecting ducts of nephrons (principal cells);

mechanism of action - intracellular receptors: enters the cell and binds to (hormone) receptors;

major actions - synthesis of proteins which are involved in Na+ transport in principal cell (epithelial sodium channels), increases sodium potassium pump activity in principal cell, increases Na+ reabsorption and decreases Na+ excretion in the urine, increases potassium excretion, increases hydrogen ion secretion in the nephron, increased blood volume and increase blood pressure;

regulation of secretion - renin-angiotensin-(hormone) system: angiotensin II and plasma potassium stimulate zona glomerulosa cells to release (hormone), ACTH had less influence on (hormone) secretion';

clinical significance - excess (hormone) causes primary or secondary hyperaldosteronism: primary hyperaldosteronism is hyper secretion from gland with low plasma renin, secondary hyperaldosteronism is due to increased renin-angiotensin mechanism: hyperaldosteronism leads to hypertension, hyperkalaemia, cardiac arrhythmia;

endocrine gland -

class -

site of production -

biosynthesis -

factors affecting release -

travels in blood -

site of action -

mechanism of action -

major actions -

regulation of secretion -

clinical significance -

angiotensin II

endocrine gland - no specific gland, synthesised in circulation.

class - peptide hormone;

site of production - synthesised in circulation;

biosynthesis - angiotensinogen to angiotensin I by renin, angiotensin I to (hormone) in the pulmonary circulation;

factors affecting release - decreased blood volume, decreased BP, decreased sodium, lead to decreased renal blood flow and increase renin, activating the RAAS system: increased blood volume, increased blood pressure, and ADH will inhibit RAAS system;

travels in blood - free form;

site of action - blood vessels, adrenal cortex, kidney, anterior pituitary, thirst centre in the hypothalamus

mechanism of action - membrane receptor, AT1 receptors, activates cAMP and phospholipase C with calcium as a second messenger;

major actions - secrete aldosterone, vasoconstriction, increased stimulation of thirst centre, increased ADH secretion, increased sodium reabsorption, increased blood volume and blood pressure;

regulation of secretion - renin-angiotensin-aldosterone system (RAAS);

clinical significance - increased renin-angiotensin system activity leads to secondary hyperaldosteronism;

atrial natriuretic peptide

endocrine gland - heart (secondary endocrine gland);

class - peptide hormone;

site of production - synthesised in the atrial (ANP) muscle in the heart;

biosynthesis - peptide hormone synthesis: begins with the transcription of the NPPA gene, producing a 151-amino acid precursor called prepro-ANP in atrial cardiomyocytes;

factors affecting release - increased ECF volume, increased blood volume, increased myocardial stretch due to increased ECF volume;

travels in blood - free form;

site of action - kidney, brain, adrenal cortex;

mechanism of action - membrane receptor: natriuretic peptide receptor and cGMP;

major actions - natriuresis: increased sodium excretion, increased water loss in urine, dilate afferent arteriole in kidney, increased glomerular filtration, decreased sodium reabsorption in the nephrons, inhibit aldosterone secretion, inhibit ADH secretion;

regulation of secretion - ECF volume and blood volume induced stretch of cardiac muscle increase (hormone) secretion, decreased stretch decrease (hormone) secretion;

clinical significance - a key diagnostic biomarker for heart failure and in guiding the development of cardiovascular therapies;

calcitonin

endocrine gland - thyroid gland;

class - peptide hormone;

site of production - parafollicular cells, or C cells of the thyroid gland;

biosynthesis - peptide synthesis;

factors affecting release - major stimulus: increased plasma calcium concentration;

travels in blood - free form, dissolved in plasma;

site of action - intestine, bone, kidney;

mechanism of action - membrane receptors, activating cAMP as second messenger;

major actions - maintains plasma ionised calcium, inhibits osteoclastic action to decrease bone resorption, increased deposition of calcium in the bone, increased renal calcium excretion, increased urinary excretion of phosphate, (hormone) receptors on osteoclasts;

regulation of secretion - blood calcium level regulates secretion via negative feedback mechanism;

clinical significance - use as a tumour marker for medullary thyroid cancer and its pharmacological use to inhibit bone resorption in conditions like osteoporosis, Paget's disease, and hypercalcemia;

cortisol

endocrine gland - adrenal gland;

class - steroid hormone;

site of production - adrenal cortex, zona fasciculata (majority) and zona reticularis;

biosynthesis - steroid biosynthesis, from cholesterol to pregnenolone and through (hormone) biosynthesis pathway, very little storage of hormones as they are synthesised on demand;

factors affecting release - stress, trauma, infection, pain leads to CRH-ACTH-(hormone) release;

travels in blood - bound form: transcortin or corticosteroid-binding globulin (CBG), and small amounts bound to globulin;

site of action - liver, skeletal muscle, and adipose tissue;

mechanism of action - intracellular receptor, enters the cell and bind to glucocorticoid receptors;

major actions - increases gluconeogenesis and plasma glucose levels, increase hepatic glucose output, increases fat mobilisation, increased protein catabolism, permissive effects on glucagon and catecholamine effects, increases anti-inflammatory cytokine production, reduces immunity, increased red cells, protects against deleterious effects of various stress

regulation of secretion - hypothalamic-pituitary-adrenal axis, negative feedback effect, CRH from hypothalamus stimulates ACTH from pituitary, stimulates (hormone): (hormone) shows diurnal rhythm in secretion, peak secretion early in the morning (with ACTH);

clinical significance -hypercortisolism: excessive secretion of ACTH (pituitary Cushing’s syndrome), primary hypercortisolism (Cushing’s syndrome), ectopic Cushing’s syndrome, primary adrenocortical insufficiency in Addison’s disease;

epinephrine and norepinephrine

endocrine gland - adrenal gland;

class - catecholamine hormone;

site of production - adrenal medulla, modified sympathetic ganglia, 90% (hormone a) and (hormone a) producing cells;

biosynthesis - synthesised from the amino acid tyrosine: tyrosine to DOPA to (hormone b) to (hormone a);

factors affecting release - stress: sympathoadrenal stimulation, sympathetic stimulation increases adrenal medullary secretion through acetylcholine transmitter;

travels in blood - free form;

site of action - heart, liver, blood vessels and other organ systems;

mechanism of action - membrane receptors, alpha and beta adrenergic receptors;

major actions - activates fight/flight mechanism, mobilises fuels from energy stores, promotes digestive processes and energy production for emergencies, increased blood glucose by glycogenolysis, gluconeogenesis, lipolysis, bronchodilation, vasoconstriction, increased heart rate and blood pressure;

regulation of secretion - sympatho-adrenal stimulation increases adrenal catecholamine secretion;

clinical significance - pheochromocytoma, excessive production and release of catecholamines, hypertension, headache, tachycardia';

follicle stimulating hormone

endocrine gland - anterior pituitary;

class - protein hormone (glycoprotein);

site of production - gonadotrophs of anterior pituitary;

biosynthesis - protein biosynthesis: preformed and stored in vesicles;

factors affecting release - gonadotropic releasing hormone (GnRH) from the hypothalamus;

travels in blood - free form with no binding protein;

site of action - sertoli cells in testis, granulosa cells of follicles in the ovary;

mechanism of action - membrane receptors with cAMP second messenger;

major actions - production of androgen binding protein in testis, causes sertoli cells to synthesise oestrogens and inhibins: inhibins, activins, and oestrogen from granulose cells in the ovary;

regulation of secretion - negative feedback mechanism, oestrogens and progesterone induced inhibition of GnRH and (hormone), inhibins induced inhibition of (hormone);

clinical significance - diagnosing infertility, evaluating ovarian reserve, investigating puberty disorders, and assessing pituitary or hypothalamic dysfunction;

glucagon

endocrine gland - pancreas;

class - peptide hormone;

site of production - alpha cells of pancreatic islets of langerhans;

biosynthesis - peptide synthesis;

factors affecting release - stimulus: hypoglycaemia, amino acids, fasting, exercise, inhibition: fatty acids, somatostatin;

travels in blood - circulates unbound;

site of action - liver, muscle, adipose tissue, peripheral tissues;

mechanism of action - membrane receptor with second messenger cAMP;

major actions - increases blood glucose, hyperglycaemic hormone, increases glycogenolysis, increases gluconeogenesis, increases lipolysis, increases fatty acids available for other tissues (ketogenic);

regulation of secretion - hypoglycaemia increases (hormone) release and hyperglycaemia decreases (hormone) release;

clinical significance - the body's primary counter-regulatory hormone to insulin, making it a critical tool for treating severe hypoglycemia and an important diagnostic and pathophysiological marker;

growth hormone

endocrine gland - anterior pituitary;

class - protein (structurally related to prolactin);

site of production - somatotrophs of anterior pituitary;

biosynthesis - protein biosynthesis: preformed and stored in vesicles;

factors affecting release - GHRH from the hypothalamus increases, somatostatin (GHIH) inhibits, increased by hypoglycaemia, acute stress, ghrelin, deep sleep, amino acids, decreased by hyperglycaemia, cortisol, IGF-I and free fatty acids;

travels in blood - free and bound form: a small amount will be bound to (hormone) binding protein which is a part of the receptor;

site of action - all tissues;

mechanism of action - membrane receptors, receptor dimerization, tyrosine kinase type of receptor to JAK-STAT pathway;

major actions - increased blood glucose, increased hepatic glucose output, increased insulin insensitivity, increased protein synthesis, increased amino acid uptake, increased lipolysis, stimulates IGF production, increased linear growth, deposition of new bone-increased chondrocyte proliferation, stimulation of osteoblasts;

regulation of secretion - controlled by the hypothalamic secretion of GHRH and somatostatin, (hormone) and IGF-I feedback on pituitary and hypothalamus to increase somatostatin and decrease GHRH (negative feedback);

clinical significance - decreased before puberty leads to dwarfism (African pygmies and Laron syndrome), increased before puberty leads to gigantism, increased after epiphyseal closure leads to acromegaly (enlargement of membranous bones);

insulin like growth factor

endocrine gland - liver: hepatocytes, bones and other cells;

class - peptide;

site of production - secreted by the liver and other tissues in response to GH stimulation;

biosynthesis - protein biosynthesis;

factors affecting release - secretion increased by GH and nutrient supply, decreased by GH regulating factors, BUT secretion is independent of GH before birth;

travels in blood - carrier proteins in the blood, IGFBP3;

site of action - many growing tissues;

mechanism of action - membrane receptors: tyrosine kinase receptor (IGF1 and 2 receptors);

major actions - cellular proliferation, differentiation, and cellular metabolism, stimulate the growth of bones, cartilage, and soft tissue, stimulate osteoblast replication and collagen and bone matrix synthesis, increased protein synthesis;

regulation of secretion - similar to GH regulation, hypothalamic-pituitary-(hormone) axis, high blood levels of (hormone) decrease secretion of GH by directly suppressing the somatotrophs, and by stimulating the release of GHIH;

clinical significance - decreased (hormone) formation leads to African pygmies where GH secretion is normal, in laron dwarfs GH levels are normal to high but no (hormone) in response to GH;

insulin

endocrine gland - pancreas;

class - peptide hormone;

site of production - beta cells of pancreatic islets of langerhands;

biosynthesis - peptide synthesis: preproinsulin to proinsulin to (hormone) and c-peptide, two polypeptide chains: A chain and B chain linked by 2 disulfide linkages;

factors affecting release - increased secretion by hyperglycaemia, increased amino acids, GH, cortisol, free fatty acids, decreased secretion by hypoglycaemia, fasting, somatostatin, in hyperglycaemia, glucose enters the cell through GLUT-2, increasing ATP, closing K+ channels, depolarisation, calcium entry, insulin release by exocytosis;

travels in blood - circulates unbound;

site of action - liver, muscle, adipose tissue, peripheral tissues;

mechanism of action - membrane receptor: tyrosine kinase receptor, signal molecule activates a cascade of kinases;

major actions - increased conversion of glucose to fatty acids in liver, increased amino acid uptake and protein synthesis in muscle, increased lipogenesis in adipose tissue, increased potassium uptake in cells, only hypoglycaemic hormone, net effect is decrease in blood glucose, inhibits gluconeogenesis, lipolysis, glycogenolysis, proteolysis, stimulates or inserts GLUT4 in muscle and adipose tissues;

regulation of secretion - hyperglycaemia leads to increase in insulin release and hypoglycaemia decreases insulin release, somatostatin from pancreas inhibits insulin release;

clinical significance - type 1 diabetes mellitus: beta cell destruction leading to insulin deficiency, type 2 diabetes mellitus: insulin secretory defect on the background of insulin resistance, both leading to hyperglycaemia, polyuria, polydipsia, and polyphagia;

luteinising hormone

endocrine gland - anterior pituitary;

class - protein hormone (glycoprotein);

site of production - gonadotrophs of anterior pituitary;

biosynthesis - protein biosynthesis, preformed and stored in vesicles;

factors affecting release - gonadotropic releasing hormone (GnRH) from hypothalamus;

travels in blood - free form, no binding protein;

site of action - interstitial cells (Leydig cells) in testis, theca cells of follicles and granulosa cells of follicles in the ovary;

mechanism of action - membrane receptors with cAMP second messenger;

major actions - production of testosterone, oestrogens, progesterone, (hormone) surge for ovulation;

regulation of secretion - negative feedback mechanism, oestrogens induced inhibition of GnRH and (hormone), androgens induced inhibition of (hormone);

clinical significance - assessing fertility, tracking ovulation, diagnosing pituitary gland disorders, and investigating early or delayed puberty in children;

oxytocin

endocrine gland - posterior pituitary;

class - peptide (nanopeptide);

site of production - synthesised in the magnocellular neurons (supraoptic and paraventricular neurons);

biosynthesis - protein biosynthesis, preformed and stored in vesicles in the posterior pituitary;

factors affecting release - stimulated during breastfeeding (lactation), and childbirth (parturition), neuroendocrine reflex;

travels in blood - free form with no binding protein;

site of action - myoepithelial cells of breast and myoepithelial cells in uterus;

mechanism of action - membrane receptors, (hormone) receptors to phospholipase C with calcium second messenger;

major actions - causes contraction of myoepithelial cells lining these small ducts, forcing the milk into large ducts and milk ejection, causes powerful rhythmic contractions of uterine smooth muscles, control of stress responses, analgesia, and social behaviour, clinically used to induce labour and during the post partum period to help return the uterus to it’s normal size;

regulation of secretion - neuroendocrine reflex for milk ejection and parturition;

clinical significance - an essential medication used primarily in obstetrics to induce labor, control postpartum haemorrhage, and aid in lactation;

parathyroid hormone

endocrine gland - parathyroid gland;

class - peptide hormone;

site of production - chief cells of parathyroid gland;

biosynthesis - preproPTH to proPTH to active hormone, with continuous production;

factors affecting release - decreased blood calcium increases (hormone) release and increased blood calcium decreases (hormone) release: calcium sensing receptors in parathyroid gland;

travels in blood - free form, dissolved in plasma;

site of action - intestine, bone, and kidney;

mechanism of action - membrane receptors, (hormone) receptor (PTH1R and PTH2R) with second messenger cAMP;

major actions - maintains plasma ionised calcium, increased osteoclastic action to increase bone resorption, increased calcium absorption acting with vitamin D in the intestine (indirect), increased reabsorption of calcium, increased urinary excretion of phosphate, (hormone) receptors on osteoblasts, increased formation of new osteoclasts;

regulation of secretion - blood calcium level regulates (hormone) secretion, negative feedback mechanism;

clinical significance - hypoparathyroidism: decreased calcium in the ECF, increased nervous system excitability, hypocalcaemic tetany, primary hyperparathyroidism: increased calcium in the ECF, extensive decalcification of bone, secondary hyperparathyroidism: compensation for hypocalcaemia;

prolactin

endocrine gland - anterior pituitary;

class - polypeptide, structurally related to GH;

site of production - lactotrophs of anterior pituitary;

biosynthesis - protein biosynthesis, preformed and stored in vesicles;

factors affecting release - TRH from hypothalamus, suckling during lactation, and oestradiol increases secretion, hypothalamic dopamine inhibits secretion;

travels in blood - free form with no binding protein;

site of action - mammary glands;

mechanism of action - membrane receptors, binds to a tyrosine kinase-associated receptor;

major actions - promotion of mammary growth (mammogenic effect), the initiation of milk secretion (lactogenic effect), and the maintenance of milk production (galactopoietic effect), (hormone) inhibits the synthesis and release of gonadotropin-releasing hormone (GnRH);

regulation of secretion - dopamine from hypothalamus inhibits the release of (hormone) from lactotrophs, while removal of inhibition promotes (hormone) release;

clinical significance - lactotropic adenoma leads to hyperprolactinemia, leading to decreased spermatogenesis, decreased testosterone and infertility;

thyroid stimulating hormone

endocrine gland - anterior pituitary;

class - protein hormone (glycoprotein with alpha and beta chains identical to that of LH, FSH, and hCG);

site of production - thyrotrophs of anterior pituitary;

biosynthesis - protein biosynthesis, preformed and stored in vesicles;

factors affecting release - thyrotropin releasing hormone from the hypothalamus;

travels in blood - free form with no binding protein;

site of action - thyroid follicular cells;

mechanism of action - membrane receptors with cAMP second messenger;

major actions - increased synthesis and secretion of thyroid hormones, iodide uptake, iodination of thyroglobulin, endocytosis, proteolysis, secretion of T3 and T4, hyperplasia of thyroid gland;

regulation of secretion - negative feedback mechanism: TRH stimulates (hormone) secretion, which increases T3 and T4 which inhibits (hormone) and TRH;

clinical significance - goiter, when (hormone) concentrations are elevated, thyroid stimulating immunoglobulins will cause thyroid hyperplasia by binding to (hormone) receptors;

thyroid hormone

endocrine gland - thryoid gland;

class - amine hormones;

site of production - thyroid follicular cells of thyroid gland;

biosynthesis - from iodine and tyrosine amino acids, iodination of tyrosine, mono and diiodothyronine to form tetraiodothyronine (T3) and thyroxine (T4): iodide trap-oxidation-iodination-coupling-deiodination;

factors affecting release - HPT axis, and negative feedback where T3 and T4 inhibit TRH and TSH;

travels in blood - carrier proteins in the blood, thyroxine-binding globulin and thyroxine binding prealbumin;

site of action - many growing tissues;

mechanism of action - nuclear receptors where T4 is converted to T3 in the cells, high affinity of receptors for T3;

major actions - increased BMR, increased calorigenesis, increased Na/K ATPase, increased protein catabolism, increased glucose absorption from GI tract, increased blood glucose, lipolysis, decreased cholesterol, maturation of CNS, increased reflex action, increased growth, increased HR, CO, increased red cells, increased respiration, permissive effect on catecholamines;

regulation of secretion - TRH secreted by the hypothalamus and stimulates TSH secretion by the anterior pituitary, TSH increases T3 and T4, as well as negative feedback loop;

clinical significance - hyperthyroidism: tremors, exophthalmos, increased reflexes, heat intolerance, hypothyroidism: cold intolerance, slow reflexes, myxoedema, hypothyroidism in children leads to cretinism, and goiter from enlarged thyroid gland;

dopamine

endocrine gland - hypothalamus and adrenal gland;

class - catecholamine;

site of production - dopaminergic neurons in the hypothalamus synthesise (hormone) and secrete it into the median eminence, adrenal medulla (sympathetic neurons);

biosynthesis - synthesised from the amino acid tyrosine, stored in vesicles until release;

factors affecting release - rewarding stimuli, goal anticipation, and physiological needs;

travels in blood - bound and chemically inactive;

site of action - the central nervous system and the cardiovascular system;

mechanism of action - membrane GPCR, alpha and beta-adrenergic receptors;

major actions - inhibits synthesis and secretion of prolactin by lactotropes, inhibits GnRH, increases secretion of TRH and TSH, increases GH secretion;

regulation of secretion - tightly regulated by a complex neurochemical feedback loop;

clinical significance - dysfunctions in its signalling pathways directly drive major neurological, psychiatric, and cardiovascular disorders;

somatostatin

endocrine gland - hypothalamus, pancreas, stomach/GIT;

class - protein;

site of production - hypothalamus, delta cells of the pancreas,

biosynthesis -

factors affecting release - IGF-I stimulates secretion of (hormone) from hypothalamus;

travels in blood -

site of action - somatotropes in the anterior pituitary

mechanism of action - binds to GPCR called SSTR on somatotrophs and activates Gai, which inhibits adenylyl cyclase, decrease cytosolic calcium, and diminishes the responsiveness of somatotropes to GHRH

major actions - inhibits secretion of growth hormone by somatotropes and TSH by thyrotropes, inhibits prolactin secretion, inhibits insulin, glucagon, and pancreatic polypeptide secretion, ;

regulation of secretion -

clinical significance -

thyroid hormone metabolic effects

increased protein synthesis at low levels, increased protein degradation at high levels; stimulates all aspects of carbohydrate metabolism (absorption, glycogenolysis, gluconeogenesis, and glucose oxidation), increases blood glucose levels; increases lipolysis and lipogenesis, but lipolysis exceeds lipogenesis, increases release of fatty acids from adipocytes; increases LDL receptors in liver to increase cholesterol removal, decreases plasma cholesterol, phospholipids, and triglycerides; formation of new synapses between neurons

anterior pituitary

thyroid stimulating hormone endocrine gland

glycoprotein hormone with alpha and beta chains, identical to LH, FSH, and hCG

hormone class of TSH

thyrotrophs of anterior pituitary

TSH site of production

protein biosynthesis, preformed and stored in vesicles

biosynthesis of TSH

thyrotropin releasing hormone from the hypothalamus

factors affecting release of TSH

free form with no binding protein

TSH travels in blood

membrane receptors to cAMP second messenger

TSH mechanism of action

increased synthesis and secretion of thyroid hormones

iodide uptake

iodination of thyroglobulin

endocytosis

proteolysis

secretion of t3 and t4

hyperplasia of the thyroid gland

TSH major actions

negative feedback mechanism

regulation of secretion of TSH

goiter, when TSH concentrations are elevated, thyroid stimulating immunoglobulins will cause thyroid hyperplasia by binding to TSH receptors

clinical significance of TSH

increased synthesis and secretion of cortisol and adrenal androgens

promotes conversion of cholesterol to pregnenolone

stimulates aldosterone biosynthesis to a lesser extend

major actions of ACTH

negative feedback mechanism

regulation of secretion of ACTH

ectopic Cushing’s syndrome

pituitary Cushing’s syndrome

hyperpigmentation when ATCH is in excess in Addison’s disease and pituitary Cushing’s syndrome

clinical significance of ACTH

anterior pituitary and ectopic from lung and pancreas

ACTH endocrine gland

peptide hormone

ACTH hormone class

corticotrophs of anterior pituitary

ACTH site of production

protein biosynthesis, large precursor peptide POMC produces ACTH and BLPH

ACTH biosynthesis

increased by stress, AVP

decreased by cortisol

diurnal rhythm of secretion with peak in early morning

factors affecting ACTH release

free form with no binding protein

ACTH travels in blood

all three layers of adrenal cortex, major regulator of cortisol and adrenal androgen release

ACTH site of action

membrane MC2R to cAMP second messenger

ACTH mechanism of action

anterior pituitary

LH endocrine gland

glycoprotein

LH hormone class

gonadotrophs of anterior pituitary

LH site of production

protein biosynthesis, preformed and stored in vesicles

LH biosynthesis

gonadotropin releasing hormone from hypothalamus

factors affecting LH release

free form with no binding protein

LH travels in blood

leydig cells in testis

theca and granulosa cells of follicles in ovaries

LH site of actions

membrane receptors to cAMP second messenger

LH mechanism of action

production of testosterone, estrogens, progesterone

surge for ovulation

major actions of LH

negative feedback mechanism: estrogens inhibit GnRH and LH, androgens inhibit LH

regulation of secretion of LH

anterior pituitary

FSH endocrine gland

glycoprotein

FSH hormone class

gonadotrophs of anterior pituitary

FSH site of production

protein biosynthesis, preformed and stored in vesicles

FSH biosynthesis

gonadotropin releasing hormone from hypothalamus

factors affecting FSH release

free form with no binding protein

FSH travels in blood

sertoli cells in testis

granulosa cells of follicles in the ovaries

FSH site of action

membrane receptors to cAMP second messenger

FSH mechanism of action

production of androgen binding protein in testis

causes testicular sertoli cells to synthesise estrogens and inhibins

causes granulosa cells to release inhibins, activins, and estrogen

major actions of FSH

negative feedback mechanism: estrogens and progesterone inhibit GnRH and FSH, inhibins inhibit FSH

regulation of FSH secretion

Anterior Pituitary

Prolactin Endocrine Gland

Polypeptide- that is structurally related to GH

Prolactin Hormone Class

Lactotrophs of Anterior Pituitary

Prolactin Site of production

Protein Biosynthesis, preformed and Stored in vesicles

Prolactin Biosynthesis

Increases: TRH, oestradiol, suckling during lactation

Decreases: hypothalamic dopamine

Prolactin Factors Affecting Release

Free form with no binding protein

Prolactin Travels in Blood

Mammary glands

Prolactin Site of actions

Membrane receptors and binds to a tyrosine kinase–associated receptor

Prolactin Mechanism of action

Promotion of mammary growth (mammogenic effect), the initiation of milk secretion (lactogenic effect), and the maintenance of milk production (galactopoietic effect); Prolactin inhibits the synthesis and release of gonadotropin-releasing hormone (GnRH)

Prolactin Major Actions

inhibition from dopamine

Prolactin Regulation of Secretion

Lactotropic adenoma - hyperprolactinemia

Hyperprolactinemia in males – decreased spermatogenesis, decreased testosterone, infertility

Prolactin Clinical Significance

Anterior Pituitary

Growth Hormone Endocrine Gland

Protein - that is structurally related to Prolactin

Growth Hormone Hormone Class

Somatotrophs of Anterior Pituitary

Growth Hormone Site of production

Protein Biosynthesis – Preformed and Stored in vesicles

Growth Hormone Biosynthesis

GHRH from the hypothalamus –increases GH; Somatostatin (GHIH) from hypothalamus decreases GH

Increased GH secretion  Hypoglycemia, acute stress, ghrelin, deep sleep, amino acids; Decreased GH secretion Hyperglycemia, cortisol, IGF-1, FFA

Growth Hormone Factors Affecting Release

Free form and bound form; a small fraction will be bound to growth hormone binding protein, which is part of GH receptor

Growth Hormone Travels in Blood

All tissues

Growth Hormone Site of actions

Membrane receptors – receptor dimerization – Tyrosine kinase type of receptor- JAK-STAT pathway

Growth Hormone Mechanism of action

Increased: blood glucose, hepatic glucose output, insulin insensitivity, protein synthesis, amino acid uptake, lipolysis, IGF production, linear growth, deposition of new bone, chondrocyte proliferation, stimulation of osteoblasts

Growth Hormone Major Actions

Hypothalamus controls GH by secreting GHRH and somatostatin; Increased GH and IGF-1 - feedback on pituitary and hypothalamus to increase somatostatin and decrease GHRH –Negative feedback (Hypothalamic-pituitary-growth axis)

Growth Hormone Regulation of Secretion

Decreased before puberty-dwarfism (African pygmies & Laron type); Increased before

Growth Hormone Clinical Significance

Posterior Pituitary

ADH Endocrine Gland

Peptide - nanopeptide

ADH Hormone Class

Synthesized in hypothalamus (supraoptic and paraventricular nucleus) – released from posterior pituitary

ADH Site of production

Protein Biosynthesis

prepro to prohormone and active vasopressin

stored in vesicles in axon terminals

ADH Biosynthesis

Increased secretion - Increased osmolarity, decreased ECF volume, Angiotensin II, Pain, stress;

Decreased secretion - Decreased osmolarity, alcohol, ANP

ADH Factors Affecting Release

Free form – No binding protein

ADH Travels in Blood

Kidney – Nephron-collecting duct (Principal cell); Blood vessels

ADH Site of actions

Membrane receptors – V2 receptor in the kidneycAMP; V1a receptor in the blood vessel

ADH Mechanism of action

Increased water reabsorption in the collecting ducts by inserting aquaporin 2 water channels; Increased blood vessel constriction (vasopressor effect);

ADH Major Actions

Osmosensitive neurons

Water ingestion suppresses osmoreceptor firing and shuts off ADH release

Change in blood pressure impacts atrial receptors and regulates ADH

ADH Regulation of Secretion