Receptor Insulin

Hormone

Location

stimulation

Corticotr opin releasing hormone

Paraventric ular nuclei of hypothala mus -anterior pituitary

Stress

-secreted into the primary capillary plexus of the hypophyseal portal system in the median eminence of the hypothalamus

CRH

-ACTH binds to receptor; g protein alpha subunit activates adenylyl cyclase increase levels of cAMP

ACTH

inhibition

Mode of action

-cAMP activates protein kinase -protein kinase activates cholesteryl ester hydrolase which converts cholesteryl esters (from LDL) into cholesterol -cAMP also activates steroidogenic acute regulatory protein which mediates the transport of newly liberated cholesterol into the mitochondria -in the mitochondria and ER cholesterol is converted into the steroid hormones

effects

-steriodogenesis

Times of secretion

Cortisol

Adrenal cortex: zona fasciculate and zona reticularis

-ACTH (produced from cleavage of POMC) -stress

-in circulation, cortisolis bound to CBG

-↓ CRH, and ADH

-disassociates from protein and diffuses across cell membrane

-↑ in appetite

-binds to cytoplasmic receptor causing receptor disassociation from HSP70, HSP90, and IP -horome-receptor complex diffuses into nucleus and activates or inhibits transcription -time delay because mechanism of action affects transcription

-maintain sensitivity to vasoconstrictors - ↑ gluconeogenesis in liver -fetal lung development -↓ACTH -↑GFR -↑ bone reabsorption -↓ insulin sensitivity -immune system suppression -↓collagen synthesis

Muscles ↑ protein degradation ↓protein synthesis ↓glucose utilization ↓sensitivity to insulin

Liver ↑glycogen storage ↑gluconeo by ↑ activity and amount of enzymes

Fat ↓glucose utilization ↓sensitivity to insulin ↑lipolysis (oxidation of fatty acids)

-high in early morning -low in late evening -when change sleeping habits, the cycle changes

↑ fat mobilization which ↑ their utilization for energy

GHRH

GH

Ventomedi al nucleus of hypothala mus Anterior pituitary

GH glucocorticoi ds

-binds to receptor activating adenylyl cyclase causing an increase in cAMP which increases transcription to make new GH and causes an influx of Ca to cause fusion of GH secretory vesicle with membrane

-amino acids

-glucose

-causes growth of almost all tissues

-starvation

-GH

-hypoglycemia

-IGF-1

-promotes increased size of cell and increased mitosis with devo of greater number of cells

-exercise

-cortisol

Adipose tissue

-stage ¾ sleep

-somatostati n

↓glucose uptake

-gonadal steroids/thyroid hormone

↑lypolysis ↓adiposity Fat used instead of carbs for E

-pulsatile pattern

Liver ↑gluconeogenesis ↑IGF-1

Muscle ↓glucose uptake ↑amino acid uptake ↑protein synthesis ↑lean body mass ↓catabolism of proteins

IGF-1

liver

GH

Muscle ↓glucose uptake ↑amino acid uptake ↑protein synthesis ↑lean body mass ↓catabolism of proteins

Bone, heart, lung ↑protein synthesis ↑DNA, RNA expression ↑cell size/number ↑organ size ↑organ function

Chondrocytes ↑amino acid uptake ↑ protein synthesis ↑ DNA, RNA expression ↑collagen ↑chondroitin sulfate ↑cell size/number ↑linear growth somatost atin

hypothala mus

TRH

Hypothala mus

TSH

Pituitary

IGF-1

-inhibits release of GH from pituitary

glucocorticoids Stimulates release of TSH from pituitary

TRH

thyroid hormone

-activates phospholipase second messenger system in pituitary to produce large amounts of phospholipase C, Ca2+, and DAG leading to TSH release 1. TSH stimulates iodide pump on basal membrane of follicular cell resulting in iodide trapping 2. peroxidase on apical membrane oxidizes iodide to iodine so it can readily bind to tyrosine of thyroglobulin in the colloid 3.ER and golgi synthesize and secrete thyroglobulin 4.in colloid, iodine binds with the aid of iodinase to tyrosine residues of thyroglobulin 5.T3 ad T4 are cleaved from thyroglobulin, pinocytic vesicles grab chunks of colloids 6. lysosomes with proteases digest TG releasing T3 and T4 that diffuse across the base of the cell into capillaries 7. everything else is recycled back to the

-causes proliferation of thyroid gland ↑ proteolysis of thyroglobulin stored in follicles ↑ activity of iodide pump ↑iodination of tyrosine t form thyroid hormone ↑size and activity of thyroid cells ↑number of thyroid cells and change from cuboidal to columnar

colloid

T4 and T3

Thyroid gland

TSH

-circulates bound to proteins -T3 binds thyroxine binding globulin and albumin -T4 binds thyrozine binding globulin, albumin, and thyroxine pre-albumin (transyrethin) --slow onset and long duration of action because tightly bound and acts through transcription and translation

↑cardiac output, tissue blood flow, HR, respiration, contractility

↑basal metabolic rate ↑mitochondria (↑ rate of formation of ATP to energize cellular function) ↑Na/K ATPase (active transport of ions) ↑O2 consumption ↑glucose absorption/uptake

-at target T3 and T4 diffuse across membrane -T4 is deiodinated to T3 which is more biologically active

Beta cells of pancreas

Glucose Amino acids Fatty acids GH/cortisol (indirect) GI hormones (amplifier)

somatostatin

↑glycogenolysis ↑lipolysis

-T3 diffuses into nucleus where it binds to receptor which is bound as a heterodimer to retinoid X receptor

↑protein synthesis

-hormone bound receptor binds to hormone response element

↑adrenergic responses (↑sensitivity to sympathetic; beta receptor activity; receptor numbers in heart,liver,muscle,adipocytes, G alpha expression)

-results in increase or decrease in transcription of genes

Insulin

↑gluconeogenesis

-synthesize as a preprohormone by RER and then cleaved in ER to form proinsulinand cleaved again in Golgi to form insulin and c peptide

-promote growth and devo of fetal brain ↑glucose transport by ↑ GLUT4 receptors on membrane ↑protein synthesis (more permeable to amino acid) ↑fat synthesis and storage

-insulin binds to receptor (4 subunits help together by disulfide bonds)

↓gluconeogenesis in liver

-binding causes beta subunits to undergo

↑ glycogen storage (inactivates liver phospholipase so no splitting of glycogen

-during meals

Fed state

autophosphorylation which activates tyrosine kinase

↑glycolysis ↑ growth and gene expression

-tyrosine kinase p-lates insulin receptor substrates (intracellular enzymes) Plasma ↓glucose ↓FFA ↓ketoacids Glucagon

Alpha cells of pancreas

Amino acids

Glucose

Acetycholine

Insulin

Ep/NE

Glucagon like peptide Leptin

Gut

Somatostatin

VIP

Ketones

CCK

FFA

-activates adenylyl cyclase in hepatic cell membrane -increase in cAMP

↓amino acids ↑blood glucose ↑ break down of glycogen ↑gluconeogenesis from a.a.

-activates protein kinase which leads to de p-lation and degradation of glycogen releasing glucose

Fasting state Feeding

↑ insulin response to glucose; amplifier ↑beta cell mass

Released from adipocytes

Increased fat

-acts on hypothalamus

↑ satiety

-causes ↓ production of NPY and AGRP

↓hunger

-activation of POMC and alpha MSH -↑CRH to ↓ food intake -↑sympathetic activity Ghrelin

Released from GI tract

fasting

PTH

Chief cells of parathyroi d

Low plasma Ca

-↓ insulin -acts within hypothalamus

High plasma Ca

Ca binds to receptor which activates an inhibitory g protein that decreases activity of adenylyl cyclase and cAMP which decreases PTH released

↑hunger

-Ca and PO4 resorption from bone -↓Ca excretion from the kidneys

Peak just before eating and falls after meal

↑renal phosphate excretion that overrides the resorption from bone GnRH

LH

Hypothala mus

Released from pituitary

-stimulates formation of 1,25 OH2D3 -stimulates pituitary to release FSH and LH

Progesterone

puslatile

-possible estrogen -GnRH Midcycle -estrogen

-testosterone Follicular phase -estrogen

-use cAMP messenger system -acts on Theca cells resulting in the production of androgens

Luteal Phase

-stimulates ovulation of ripe follicles and formation of corpus luteum

-peak in utero for oogonia devo

-stimulates leydig cells to synthesize and secrete Testosterone

-surge prior to ovulation

-stimulates growth of follicle and estrogen in females

-peak in utero for oogonia devo

-acts on sertoli cells to promote maturation of sperm

-peak 6 months for final sexual differenti ation

Progesterone

-hCG FSH

Released from pituitary

-GnRH Midcycle -estrogen

-testosterone Follicular phase -estrogen

Luteal Phase

-uses cAMP messenger system -acts on the granulose cells resulting in synthesis of pregnenolone which is give to theca cells and production of aromatse to convert androgens that the theca produce to make estradiol and estrone

Progesterone

-hCG -inhibin Estrogen s: βestradiol; estrone; estriol

Ovaries, corpus luteum

FSH/LH

-promotes proliferation and growth of specific cells in the body responsible for devo of secondary sex characteristics

-cause autocrine affects to first increase sensitivity to FSH by increase receptors and then icnreaseing LH receptos ↑cilia formation and activity of the oviduct lining ↑contractility of muscular wall ↑proliferation of the endometrium ↑growth and contractility of the myometrium ↑epithelial proliferation and glucogen deposition in vagina -watery secretion of cervical glands -inhibits osteoclastic activity to promote bone growth preventing osteoporesis ↑secretion of oviduct lining

progester one

↓contractility of muscular wall ↑differentiation and secretion of endometrium ↓contractility of myometrium ↑epithelial differentiation of vagina ↓epithelial proliferation of vagina

hCG

Placenta (syncytial trophoblast cells)

HCS/HPL

Palcenta

-dense, viscous secretion from cervical glands -causes persistent corpus luteum to prevent menstruation by continuing to secrete estrogen and progesterone -causes endometrium to continue to grow and store large amounts of nutrients -partial development of breast and maybe lactation in animals -similar to GH but need lots of HPL to promote growth -↓ insulin sensitivity and ↓ utilization of

Peaks first trimester

glucose in mother making more available for the baby (hyperglycemia)

Oxytocin

Posterior pituitary

Prolactin

Anterior pituitary

Testoster one

Leydig cells

-promotoes release of FFA from mom to baby -increases uterine contractions

Hypothalamus -cervical stretch receptors Suckling pregnancy LH

-causes contraction of mammary gland alveoli for milk let down -promotes milk production and secretion into alveoli

Dopamine -enters cell, 5 alpha reductase converts to DHT -circulates bound to sex hormone binding globulin

-secondary sex characteristics; external genitalia, pigmentation, facial and body hair, prostate, voice, libido, linear growth, epiphyseal fusion

-causes transcription

DHT

-acts on sertoli cells to cause synthesis of androgen binding protein which causes a local testosterone sink that sucks up huge numbers preventing it from escaping and bathing developing sperm with huge amounts of T because increasing bound T increases free T so always in equilibrium -activates transcription

-fetal development of epididymis, vas deferens, seminal vesicles -pubertal growth of penis, seminal vesicles, musculature, skeleton, larynx -spermatogenesis -fetal development of penis, penile urethra, scrotum, prostate -pubertal growth of scrotum, prostate, sexual hair sebaceous glands -prostatic secretion

Peaks 8 weeks, one year, and puberty