Hormones Flashcards
GHRH target/effect/inhibition
somatotroph, causes release of Growth Hormone, Somatostatin/IGF
GHIH(somatostatin)
Somatotroph Inhibits GH release, upregulated by IGF
Growth hormone is ihibited by
Somatostatin (GHIH,) positive feedback from IGF and Negative feedback to stop GHRH and GH from IGF and GH on Somatotropho to stop GH.
GH release is stimulated by
GHRH from Hypothalamus – Ghrelin from hypoglycemia **Thyrone hormone is required for action of growth hormone
GH transport and metabolism
pulsatile release, travels freely or bound to GHBP, eposidic release-1/2L~20min, Bound~50 min. Broken down in liver and excreted in urine.
IGF (Somatomedin C)
related structurally to pro insulin IGF 1 most important and responds to GH Have a long half life because they bind to IGF binding proteins
IGF actions
important for growth effects of GH,– promote linear bone growth,– increase organ size and function, –insufficient synthess of IGF’s can result in dwarfism,
Prolactin is stimulated by
lack of dopamine, TRH, estradiol inhibits dopamine, sensitizes to TRH.
prolactin secretion is inhibited by
dopamine from hypothalamus
Dopamine in hypothalamus MOA
binds to Gi on lactotroph and this decreases cAMP and calcium which will prevent release of prolactin, inhibited by estradiol
ADH secretion stimulated by
mediated via baroreceptors plasma osmolarity, if you have a 1-2% change Plasma Volume decrease in at least 10% of volume
ADH MOA
increase in cAMP causes aquaporins(AP2 only) to transport to luminal membrane
ADH second messenger
binds to V2 receptor increase cAMP (Gs) Binds to V1 recptor which increases IP3 and DAG(Gq)
ADH deficiency
Diabetes insipidus
Oxytocin secertion is upregulated by
a nursing baby, pressure against the cervix during birth
Oxytocin target cells
Smooth muscle cell in breasts in and uterus, causes contraction.
TRH triggers release of/is inhibited by
TSH in the anterior pituitary/Thyroid hormones
Thyrotropin releasing hormone is made up of
a tripeptide
TRH is secreted at/
a constant rate
Thyroid Stimulating hormone effects
promotes growth of thyroid gland, stimulates all steps of thyroid hormone synthesis. Tropic effect- trophic effect- increases size of gland.
TH is made from
iodination of tyrosine molecules grouped together in thryoglobulin
TH formation
- binding of TSH to receptor will cause syntehsis of thryoglobulin which contains tyrosine residues which is extruded onto the epical membrane
- Secondary active transport of Iodine into the cell with Na and extruded onto apical side of membrane
- oxidation of I which is catalyzed by TPO
- Iodination of thyroglobulin to form MIT or DIT (25%, more DIT)
- coupling of MIT DIT or DIT DIT
- TSH causes endocytosis of Thyroglopulin and will combine with lysoendosomes and split into T3 and T4, MIT, DIT
- enters circulation.
- MIT, DIT recycled.
Inhibition of TH synthesis
perchlorate, thyocyanate, nitrates,HIGH I- inhibit sodium iodine pump –PTU Propthiouracil, will inhiibt Oxidation, organification(wolf chykoff effect, high I inhibits.) and coupling.
TSH target for
antibodies, Stimulatory in graves, blocking in hashimotos.
TSH Receptor is located
on the basolateral side and membrane.
Thyroid hormone MOA
T3 enter the cell and bind to receptor T4 will enter the cell and be converted to T3 by 5` deiodinase, both will now enter the nucleus and caue thyroid like effects
TH second messengers
in Cardiac muscle, will incrase SR Ca ATPase- incrases CO will increase NA/K ATPase – will increase Beta 1 receptors, which will increase heart rate
T3 provides negative feedback to
both the hypothalamus and thyrotroph in anterior pituitary
Zona glomerulosa
secretes aldosterone, regulated by AgII and K+
Zona fasciulata, reticularis
secretes cortisol and androgens, is regulated by ACTH
Adrenal medulla
secretes NE and E, regulated by sympathetic control.
Aldosterone regulation
hypothalamus secretes, CRH, Anterior pituatary secretes ACTH. Angiotensin, II, ACTH, K+ all act on the zona glomerulosa of the adrenal cortex to produce aldosterone.
Hypothalamic pituitary axis
Cotisol, androgens produced through CRH, ACTH, action on Zona fasciculata and reticularis.
CRH- corticotropin releasing hormone
released by PVN cells, stimulates ACTH synthesis and release, is released diurnally and pulsatile. –stimulated by stressors, catecholamines, –inhibited by ACTH
ACTH
derived from Preprohormone proopiomelanocortin (POMC) secretion is diurnal and pulsatile. – alpha MSH is contained in the sequence of ACTH
excess ACTH results in
hyperpigmentation
Mechanism of action ACTH
Gs receptor timulation, increase CAMP, k creased PKA, which leads to increased P protiens and steroidogenic enzymes. both of these act on Star protein in mitochondrion which produces pregnenolone. which goes to smooth er.
Aldosterone regulation
angiotensin II is a major regulator, ACTH is minor and increased K+ too, –Aldosterone decreases AgII and K+
K+ MOA on Glomerulosa cell
increased potassium in cell causes increased Ca which activates aldosterone synthesis.
ACTH MOA on fasciculata
cAMP increased on Gs receptor, causes phosphorylation of proteins
transport of cortisol
bound to corticosteroid binding hormone and albmin, with 4% unbound.
corticosteroid binding hormone is increased in
pregnancy due to increased estrogen, hyperthyroidism, and birth control pills.
cortisol is metabolized
in the liver and exreted in urine.
cortisol regulation
it negative feedbacks, hypothalamus and AP, ACTH also negative feedbacks the hypothlamus
Epinephrine Second messenger
Sodium and Calcium
epinephrine is triggered by
stress, hypothermia, too much exercise
Epinephrine MOA
ACH binds to Nicotinic receptor and causes sodium to go into the cell and depolarize it. This will increase calcium and cause release and synthesis of E and NE
Synthesis of NE and E
happens in cytosol except one step Tyrosine is converted to L-Dopa by Tyrosine hyrdoxylase Dopa is converted by Doapmine by Dopa decarboxylase, which will then enter a secretory granule which will have Beta hydrxoylase to convert it NE, Ne will leave the vesicle and PNMT will change it to E in the cytosol
For epinephrine to be active it requries
High concentarions of Cortisol and then will go to the vesicle to bes stored again.
Epinephrine synthesis is under the control of
CRH- ACTH cortisol due to ACTH stimulating synthesis of dopa and NE, and the major effect of cortisol from teh adrenal cortex released into circulation which also upregulates PNMT.
actions of catecholamines
increase CO, Preload, and BP, bronchodilationl, diverts blood flow and mobilizes energy store.s
Delta cells secrete
somatostatin
F cells secrete
Pancreatic polypeptide
insulin pre pro peptide made up of
A chain b chain C peptide
Pre pro hormone is cleaved at
C peptide
C peptide and insulin are released in
equalmolar concentrations.
to measure insulin measure
C-peptide.
stimulus of insulin prodcution
high levels of glucose, amino acids, catecholamines, and somatostatin
GLUT 2 transporter and release of insulin in Beta Cells.
low affinity for glucose, GLucose is transported in and it is broken down to glucose 6 phosphate by glucokinase, this prevents glucose form leaving and is the rate limiting step. it is also a glucose sensor that regulates your insulin productions to the level of glucose. increase in ADP inhibits Potassium channels(sulfanyl urea channels) This depolarizes cell and increases calcium levels which causes insulin release.
GLucagon main target cell is
liver but also can target adipose.
Glucagon is triggered by
stress and hypoglycemia, also high (some) AA in blood.
Glucagon is inhibited by
insulin
Somatostatin release triggered by
ingesting food.
Somatostatin effects( are local)
decrease insulin, glucagon secretion, GIT motility, secretions and absorption by GIT.
factors that decrease calcium levels
decrease in plasma protiens, nephrotic syndrome, malnutrition, liver disease,
Factors that increase calcium
increase in plasma protine, and multiple myeloma.
PTH is made in
the they cheif cell of the parathyroid.
PTH release is triggered by
low levels of calcium
MOA for calcium on Chief cell.
ionized calcium binds to Calcium receptor on chief cell. This is a Gq receptor that stimulates DAG and IP3 which causes an increase in Calcium intracellular. This causes inhibition of PTH release.
Actions of PTH
osteoblast, Gq receptor acivates cytokines which will act on osteoclast and you will have born resporption. Kidney- promotes reabsorption of Calciumin distal tubule and decreases tubular rabsorption of phosphate. Stomach, increases intestinal absorption of calcium.
TARGET tissues of PTH
Bone, osteoblastic cell, Kidney
Calcitriol, Vit D. 1,25 dihydroxycholecalciferol requires
PTH to be active.
skin synthesis of Vit D.
7-dehydrocholesterol–UV–>cholecalciferol–25hydroxylase–> (LIVER) 25 hydroxycholeciferol–1hydroxylase, (PTH)–>(KIDNEY) 1,25 OH cholecacliferol or –24,25hydroxylase–> d4,25 cholecalcierol
Target tissue of Calcitriol
Duodenal cell.
calbindin maintains
low intracellular calcium levels in the GIT.
in presence of VIT D in the gut calcium
calcium ravels to basal side and promotes it’s absorption, along with phosphate.
Calcitonin
secreted by c cells, of thyroid, only inportant in fetus in formation of bone
hypothalamic pituatary axis males
Hypothalamus–> GNRH–>Anterior pituatary–>LH, FSH–>Testes–>Leydig and sertoli cells.
inhibition of GNRH release in males
Sleep/wake cycle, Stress, hormones(estrogen, prolactin) temperature of testes.
GNRH-
10 peptides released in pulsatile fashion from birth to 8 years it is basal levels, and at 8-12 years of age you get an increase every one -3 hours, maximum at night. (LH mirror GNRH) (FSH is similar but has a prolonged half life and amplituded because youa re inhibiting
GNRH Target Cell
Anterior pituatary.
Target cell of LH
Leydig cells
MOA of LH
causes conversion of cholesterol to testosterone.
MOA of FSH
Gs receptor, increases DNA transcription, causes secretion of Inhibitn, aromatase, androgen binding proteins, forwth factors
FSH target cells
sertoli cells.
testosterone Target cell
Sertoli cells
testosterone effects
is converted to estradiol by aromatase in fetal testes causes formation of penis and scrotum with hCG and testicular descent, promotes spermatogenesis. promotes long bone fusion, BMR and increase in RBC mass
ABP
will bind to testosterone and move into lumen and will help the sperm be viable.
Testosterone MOA
converted to dihydrotestoserone and move to nucleus and cause modualtion of DNA
5 alpha reductase
converts testosterone to dihydrotestosterone
testosterone negatively feedbacks
hypohtalamus and anterior pituatary
inhibin acts on
the anterior pituatary to down regulate FSH and LH
target cell, MOA for LH Females
Thecal cell internal, is a Gs receptor, will promote DNA trasncription and change cholesterol to pregnenolone, late follicular phase granulosa cell
target cell MOA of FSH
early to mid follicularphase granulosa cells. cells Gs receptor, increase DNA transcripton and make enzymes
two cell cooperation of females in early to mid follicular phase
LH increases LDL receptor and pregnenolone is converted to androstenedione and it will move to granulosa cell, under FSH it iwll convert androstenedione into estadiol.
late follicular phase
cholesterol converted to pregnenolone this will make androstenedione and that will go to granular cell to make estradiol, but LH on granulosa cell makes progesterone.
estrogens feed back on
the adrenergic receptors on the hypothalamus and the anterior pituitary on the priming GNRH receptors.
Progesterone
helps LH surge, FSH surge, inhibits estrogen, aides in ovulation. inhibits hypothalamus to produce GnRH by way of beta endorphin.
estrogens,
group of steroids, Beta estradiol is the major in non pregnant and estriol is in the pregnant. cleared by the livel
progesterones
helps in proliferation of uterine epithelium, aids ovulation, promotes development of lobules and alveoli in breast, inhibites uterine excitability in pregnancy
hCG
supports corpus luteum,
Ghrelin
peptide made in fundus of stomach. binds to GH secretagogue receptor on somatrophs and causes release of GHRH. released during fasting.
