deck_716979 Flashcards
protein/peptide hormones
syn as preprohormone or pre hormonesstored in granulespolarusually in blood unboundplasma membrane receptorsnot administered orally
steroid hormone
derived from cholesterolintracellular receptorsin blood boundstored inendocrine glandsnonpolaroften orally administered
Throid hormones
derived from tyrosinecross cell membranesin blood boundintracellular receptorsstored in folliclescan be administered orally
catecholamines
derived from tyrosinecell surface receptorsstored in membrane bound granulesin blood free or loosely bound to protein
hormones via phospholipase C
GnRH, TRH, Angiotensin II, ADH, oxytocin, alpha 1 receptors
hormones via steroid hormone mech.
glucocorticoids, estrogen, progesterone, testosterone, aldosterone, vit D, Thyroid hormones
ADH action (V1 and V2)
V2 receptor - collecting ducts more permeable to water - high affinity for ADH -> sensitive to small changes in blood osmolarityV1: mesangial cell contraction in glomerulus; suppress renin release from JG’s; arteriole constriction; increase ACTH release from ant. pit. - low affinity for ADH
Oxytocin action
contraction of smooth mm via V1 receptor- contraction of mammary myoepithelium -> milk ejection- contraction of myometrium of uterus during labor- released during orgasm -> contracts uterus
pituitary blood supply
allows deliver of releasing and inhibitory factors selectively to anterior pituitary in high concentration.long portal vessels - median eminence, down pituitary stalk -> ant. pitshort portal vessels - post. pit -> ant. pit.
6 major ant. pit hormones
- FSH - gonadotrophs - promotes gamete development in both sexes. 2. LH - gonadotrophs - promotes sex steroid synthesis in both sexes. 3. TSH - thyrotrophs, stimulates growth and hormone production of thyroid gland. 4. GH - somatotrophs, promotes the overall growth of the body - both bones and soft tissue. 5. PRL - mammotrophs, is responsible for milk production in females and normal levels enhance LH action in males (note that high PRL levels are inhibitory). 6. ACTH stimulates the growth and steroid production of the adrenal cortex
hypothalamic releasing hormones
GnRH -> LH and FSH (LH is more sensitive to GnRH than is FSH)GHRH -> GH (inhibited by somatostatin (GHIH)) TRH -> TSH and PRL (inhibited by somatostatin (GHIH)) dopamine (PIH) -> inhibits PRL (stimulated by various factors (TRH, VIP, oxytocin & vasopressin).CRH -> ACTHact via G protein -> increase IP3 -> increase intracellular Ca2+
iodothyronines
formed by coupling of two iodinated thyroglobulins (via thyroid peroxidase)T4 - most abundant, acts as prohormoneT3 - active (shorter half life)rT3 - inactive (high in fetus)
Thyroid Hormone Syn
- iodine trap; Na-Cl pump (stim via TSH)2. thyroglobulin syn in thyroid RER3. Thyroglobulin and Iodide pumped into lumen4. Iodide -> Iodine (TP)5. iodination of thyroglobulin (TP)6. coupling of MIT’s and DIT’s (TP) -> thyroid hormone bound to thyroglobulin
TH release
- stim via TSH2. Endocytose colloid3. lysosomal proteases hydrolized thyroglobulin -> AA’s, T3, T4, DIT and MIT4. T3 and T4 released5. DIT, MIT and AA’s recycled into thyroglobulin and Iodide
Wolf-Chaikoff effect
excess idodine -> decrease thyroid sensitivity to TSH -> decrease TH synthesis -> hypothyroid
T4 -> T3 enzyme
5’ deiodinaseT4->rT3 - 5’ monodeiodinase
TH action
enters cell -> binds thyroid response element on target gene -> removes gene co-repressors -> gene transcriptionReceptor has higher affinity for T3target tissues have 5’ deiodinaseTarget tissues increase oxygen consumption in response except testes, brain, spleen, pituitary
Graves disease
hyperthyroid w/ low levels of TSHTSI mimics TSH action -> increase TH syn and secretion -> goiter -> negative feedback decreases TSH levels, but TSI remain high
“Hashimoto’s thyroiditis
most common hypothyroid in USantibodies against follicular cells and TSH receptors destroy thyroid functioninitially blood work shows high TSH but normal levels of T4 (compensation)
cretinism
caused by hypothyroidism in fetus till 2 yrsCretins are dwarfed, have pot-bellies, protruding tongues and are severely retarded
hypothyroid as child
stunts growth (further exasperated by low GH)often no pubertysevere mental issuesgrowth can catch up w/ TH replacement therapy, but mental issues can’t be reversed
Thyroid actions
increase BMR (O2 and fuel consumption)gluconeogenesisglycogenolysislipogenesislipolysisincreases LDL receptors -> decrease serum cholesterolprotein sythesisproteolysis -> muscle wasting (hyper)increase heat productionincrease Beta adrenoreceptors -> increase sympathetic responseincrease HR and Contractility
hypothyroid symptoms
Decreased basal metabolic rate, high cholesterole and atherosclerosis, Thick tongue, Myxedema, Weakness, fatigue, lethargy, Goiter, Somnolence, Slow speech, Mental slowness, Hoarseness, Muscle aches, Amenorrhea, Cold intolerance, Psychosis, Dry cold skin, Electrocardiogram changes, Prolonged reflex times, Constipation, Decreased sweating, Thin, brittle hair Weight gain
hyperthyroid symptoms
Nervousness, Bruit over thyroid, Anxiety, Pretibial myxedema, Insomnia (Graves’ disease), Heat intolerance, Fatigue, Palpitations, Eye problems (Graves’ disease), Muscle weakness, Exophthalmos, Diarrhea, Lid retraction, Increased appetite, Extraocular muscle weakness, Moist, warm skin, Eye irritation, Goiter Tremor
primary, secondary, tertiary hypothyroid
primary: issue in thyroid; response to TSH low, response to TRH highsecondary: issue in pituistary; response to TSH normal, response to TRH lowtertiary: issue in hypothalamus; response to TSH normal, response to TRH normal, but secretion of TRH is low
amylin
cosecreted w/ insulinsupports insulin action
C-peptide
plasma level index of insulin secretioncleaved from insulin in activation
Insulin biochem action on target tissue
binds receptor -> autophosphorylation -> activates tyrosine kinase -> phosporylation cascade.. PI3 kinase -> PKB -> activates GLUT 4 and glyocogen synthaseRAS and MAP kinase -> activate transcription factorsPLCgamma -> influx of K+, etc
insulin stimulators
GLUCOSEK+, AA’s, FFA’s, GI hormones, Beta adrenergics, Parasympathetics, glucagon
glucagon action
Liver is major target -> glycogenolysis, gluconeogenesis -> glucose generationProteolysis -> AA’s -> glucoseLipolysis -> ketoacidsALL action via cAMP
cortisol action
increasing glycogenolysis, gluconeogenesis, glycogenesis, lipolysis, and proteolysis -> hyperglycemicGlucose: glucose production (short term E); Glycogen synthesis (long term E); promotes glucagon release while inhibiting insulin actionProtein: increase proteolysis -> AA’s -> glucoseFat: lyposis in extremeties; lypogenesis in trunk and face; inhibits LDL uptakeBone: inhibits bone formation via - osteoblast; - collagen; - Vit D; + resorptionKidney: water excretion via - ADH; + GFRGI: Peptic ulcer’s via + HCL; - prolifImmune system: decreases lymphocytes; anti-inflamvascular: maintains BP
Aldosterone Synthesis
Zona GlomerulusCholesterole -> pregnolone -> progesterone (3B OH steroid dehydrogenase) -> DOC (21-hydroxylation) -> corticosterone (11-hydroxylation) -> aldosterone (aldosterone synthase)
Cortisol synthesis
Zona Fasiculata: 17-hydroxylase is uniquepregnolone -> 17 hydroxypregnolone (17-hydroxylase) -> 17-hydroxypregnolone (3B-OH SD) -> 11-deoxycortisol (21-hydroxylase) -> cortisol (11-hydroxylase)1 extra step w/ 17 hydroxylase
DHEA synthesis
Zona Reticularis: C17-20 lyase is unique17-hydroxypregnolone (from Fasiculata) -> DHEA (C17-20 lyase)
ACTH action on adrenal cortex
trophic via IGF-IIpromotes steroid syn:- increases cholesterol availability (uptake, synthesis, mobilizes stored)- increases side chain cleavages and hydroxylases activity
cushings syndrome
Hypercortisolcentripetal obesity, hypertension, hyperglycemia, amenorrhea or impotence, hirsutism, purple striae, “moon” facies, osteoporosis, easy bruisability, and personality change
cushings causes
Cushings Disease: pituitary tumor -> high ACTH -> high cortisoladrenal tumor -> high cortisol -> low ACTHectopic tumor -> high ACTH -> high cortisol
cortisol antinflammatory response
inhibits formation of arachidonic acidinhibits neutrophil functioninhibits COX2inhibits PAF productioninhibits NO production
cortisol as immunosuppresent
inhibits IL-1 -> decrease T-lymphocytesinhibits IL-2Inhibits macrophage fnct.
stress and cortisol
stress over rides negative feedback of cortisol on CRH and ACTH -> increased cortisol
aldosterone stimulators
- angiotensin II in response to low plasma osmolarity2. hyperkalemia3. stress
addisons disease
primary adrenal insufficiencyhyponatremia, hypotension, weakness (due to hyperkalemia), hyperkalemia, weight loss (anorexia, nausea, vomiting), and hyper-pigmentation
21-Hydroxylase deficiency
↓ Cortisol ,↓ Aldosterone, ↑ Androgens Masculinization, Salt loss
11β-Hydroxylase deficiency
↓ Cortisol, ↓ Aldosterone, ↑ Androgens, ↑ DOC Masculinization (mild), Hypertension
17α-Hydroxylase deficiency
↓ Cortisol, ↓ Androgens & estrogens, ↑ DOC & corticosterone, ↑ AldosteroneHypertension, Hypokalemic, alkalosis, Sexual infantilism
Conn’s Syndrome
primary hyperaldosteronism -> aldosterone-secreting tumor. increased ECF volume, hypertension, hypokalemia, and metabolic alkalosis.
catecholamine biosynthesis
Tyrosine → DOPA → DA → NE → E- Tyrosine hydroxylase(tyr→ DOPA) = rate limiting enzyme (negative feedback inhibited; neuroligically stimulated)- Dopamine β-hydroxylase (DA → NE) is the only enzyme located in the granules – the rest of the enzymes are cytosolic.- PNMT (NE → E) is found only in epinephrine producing cells (stim via cortisol)
catecholamine metabolism product
2 pathways - both result in VMA -> excreted in urine
fight of flight response
Adrenal Cortex and Medulla work togethermedulla epinephrine -> immediate and intense responseCortical cortisol -> takes hours for response to take place
catecholamine receptors
Alpha 1: equal affin for nor and epi; post synaptic terminals -> excitatory (+ IP3, DAG)Alpha 2: equal affin for nor and epi; pre synaptic terminal; inhibitory (-cAMP)Beta 1: equal affin; heart; excitatory (+cAMP_Beta 2: greater affin for epi; liver; excitatory (+cAMP)
epi on cardiovascular
heart: + HR and Contractility via B1 Arterioles: constrict splanchnic, renal, cutaneous via alpha 1 and dilate muscle arterioles via B2norepi decreases heart rate
epi on metabolism
Epi is antiinsulin, diabetogenic, ketogenicGets glucose and fuel into blood stream
Symptoms of Pheochromocytoma
Hypertension 90 Severe headache 80 Excessive perspiration 70 Palpitations with or without tachycardia 65 Nausea 40 Tremor 30 Weakness, exhaustion, fatigue 30 Anxiety, nervousness 25 Abdominal pain 20 Blurred vision 10
fetal growth
- directly controlled by GF mediated by IGF-II- independent of hormonal control w/ exception of Insulin -> increases growth- peaks mid gestation
postnatal growth (0-2)
RapidGH rises -> IGF-II risesIGF-I levels are lowThyroid Hormone very important
3-4 yrs growth
IGF-I increases and peaks at puberty - plays central role in childhood growth
puberty growth
Gonadal hormones play important role
GH action
increases lean body massdirect action on adipose (decreases), muscle (increases), liverindirect action via IGFs (somatomedins) from liveradipose: + lipolysis; - glucose uptakemuscle: + AA transport, + protein syn, - glucose uptakeLiver: + glucose output, + FA ox, + ketogenesis, + IGF’s
GH regulation
From hypthalamus:- GHRH stimulates- Somatostatin inhibitsNegative feedback from GH and somatomedin stimulate somatostatin releasestimulated by: Sleep, exercise, hypoglycemia, high AA’s, estrogeninhibits: high FFA (obesity), hyperglycemia
hypocalcemia
muscle tetany -> increases permeability of Na -> depolarizes -> twitching
hypercalcemia
lethargytissue calcificationdiuresis
PTHrp
mimics PTH-> increases plasma Ca -> not effected by the - feedback - feedback decreases PTH levels
PTH action
Bone resorptionrenal reabsorption of Carenal excretion of Phosphateactivates Vit D -> increase gut resorption of Caaction via cAMP
calcitonin
defense against sudden Ca load -> slight bone depostion of Ca
Vit. D
2 sources: diet, 7-dehydrocholesterolUV light changes 7-deh. -> cholecalciferol (dietary Vit D) Liver: Cholecal. -> 25-OH chole.Kidney: activates+ blood Ca, + phosphate
