Endocrine Physiology Flashcards
Preprohormone
synthesis occurs in ER and is directed by mRNA
Prohormone
preprohormone with the signal peptides cleaved, transported to the Golgi apparatus
Hormone
finished being modified in Golgi
Amine hormones
derivatives of tyrosine
thyroid hormones, epinephrine, NE
Negative Feedback
hormone that can directly or indirectly inhibit further secretion of hormone
Positive Feedback
explosive and self-reinforcing
Ex. LH with estrogen
A hormone that decreased the number or affinity of receptors for itself or for another hormone
Down-regulation
Ex. Progesterone downreg its own receptor and receptor for estrogen
A hormone that increases the number or affinity of receptors for itself or for another hormone
Up-regulation
Ex. estrogen up-reg its own receptor and receptor for LH on ovaries
Hormones that use cAMP Mechanism
FSH, LH, ACTH, ADH (V2), HCG, MSH, CRH, B1 and B2, Calcitonin, PTH, Glucagon
Hormones that use IP3 Mechanism
GnRH, TRH, GHRH, AngII, ADH (V1), Oxytocin, alpha-1
Steroid Hormone Mechanism
Glucocorticoids, Estrogen, Testosterone, Progesterone, Aldosterone, Vit D, Thyroid Homrone
Activation of Tyrosine Kinase
Insulin and IGF-1
Uses cGMP
ANP, EDRF, Nitric Oxide
Uses Hypothalamic-hypophysial portal system
anterior lobe of pituitary
cell bodies for posterior lobe of pituitary
in hypothalamic nuclei
Produced by a single pro-opiomelanocortin (POMC)
ACTH, MSH, beta-lipotropin and beta-endorphin
Causes increased secretion of Growth Hormone
sleep, stress, puberty hormones, starvation, exercise, and hypoglycemia
Causes decrease in Growth Hormone
somatostatin, somatomedins, obesity, hyperglycemia, and pregnancy
Somatomedins
produces when GH acts on target tissues
inhibit the secretion of growth hormone by acting directly on anterior pituitary and stimulating secretion of somatostatin
Factors that increase Prolactin secretion
estrogen during pregnancy, breast-feeding, sleep, stress, TRH, DA antgonists
Factors that decrease Prolactin secretion
dopamine, bromocriptine, somatostatin, Prolactin from negative feedback
Supraoptic nuclei
where ADH originates
Paraventricular nuclei
where Oxytocin originates
CRH containing neurons
Causes ejection of milk from breat
Oxytocin
dilation of cervix and orgasm
increase secretion of oxytocin
Can be used to induce labor and reduce postpartum bleeding
Oxytocin
inhibit iodide pump and Na-I cotransport
thiocyanate and perchlorate anions
iodide into I2
peroxidase enzyme in the follicular cell membrane
propylthiouracil
inhibits peroxidase enzyme to treat hyperthyroidism
Organification
Tyrosine residues of thyroglobulin react with I2 to form MIT and DIT
Inhibits Organification
high levels of iodide (I-) inhibit organification
Wolff-Chaikoff Effect
DIT + DIT
makes thyroxine (T4) T4 is more prevalent but T3 is more active
MIT+DIT
makes triiodothyronine (T3) T3 downregulates TRH receptors
Thyroid deiodinase
deiodinates leftover MIT and DIT, if deficient in this enzyme, it will mimic iodine deficiency
Liver Failure and Thyroid Hormone
Liver failure causes a decrease in TBG leading to decrease in total thyroid hormone levels, but normal levels of free thryoid
Pregnancy and Thyroid Hormone
TBG levels increase leading to an increase in total thyroid hormone levels, normal levels of free hormone
5’-iodinase
converts T4 into T3 or rT3 (rT3 is inactive)
Grave’s Disease
thyroid stimulating antibodies
low conc of TSH
hyperthyroidism
Actions of Thyroid Hormone
promote bone formation
matures CNS in perinatal period
up-regulates B1 in the heart, increase CO
increases syn of Na/K-ATPase
glycogenolysis, gluconeogenesis, glucose oxidation, lipolysis, catabolic protein
listlessness, slowed speech, somnolence, impaired memory, and decreased mental capacity
hypothyroidism
Cretinism
Congenital Hypothyroidism
Myxedema
Hypothyroidism
Exophthalamos
Hyperthyroidism
Zona glomerulosa
makes aldosterone
Zona fasciculata
makes glucocorticoids (cortisol)
Zona Reticularis
makes androgens like dehydroepiandrosterone and androstenedione
21-Carbon steroids
progesterone, deoxycorticosterone, aldosterone, and cortisol
Hydroxylation of C21 of progesterone
makes deoxycorticosterone (a mineralocorticoid)
Hydroxylation of C17 of progesterone
makes cortisol (a glucocorticoid)
19 Carbon Steroids
have androgenic activity and are precursors to estrogen
18 Carbon Steroids
have estrogenic activity
Oxidation of A ring (aromatization) priduce estrogen occurs in ovaries and placenta
Cortisol levels for people who sleep at night
highest just before waking (~8am) and lowest in the evening (~12am)
precursor to ACTH
POMC which is synthesized when CRH binds corticotrophs in anterior pituitary
Cholesterol desmolase
stimulated by ACTH to increase steroid synthesis
Dexamethasone Suppression test
based on the ability of dexamethasone to inhibit ACTH secretion
- normal people: ACTH will be suppressed
- ACTH-sercreting tumors: high-dose dexa suppresses it
- adrenal cortical tumors: no dex can inhibit cortisol secretion
Aldosterone
under tonic control by ACTH and separately regulated by RAS
used to increase blood volume by reabsorpting Na and secrete K and H
Glucocorticoids in response to stress
stimulates gluconeogenesis, they increase protein catabolism, decrease glucose utilization and insulin sensitivity in adipose, increase lipolysis
Glucocorticoids anti-inflammatory effects
Induce syn of lipocortin and inhibitor of phospholipase A2
inhibit production of IL-2 and prolif of T cells
inhibit release of histamine and serotonin
Glucocorticoids and the suppression of the immune system
inhibit the production of IL-2 and T cells
Glucocorticoids and vascular responsiveness to catecholamines
cortisol up-regulates alpha-1 receptors on arterioles, increasing their sensitivity to the vasoconstrictor effect of NE
Addison’s Disease
Primary Adrenocortical Insufficiency
increased ACTH, hypoglycemia, hyperpigmentation, decreased pubic and axillary hair
Wt loss, Weak, N/V
Secondary Adrenocortical Insufficiency
Caused by primary deficiency of ACTH
only cortisol levels are low
fatigue, muscle weakness, wt loss
Cushing Syndrome
Primary adrenal hyperplasia.
produces elevated glucocorticoid levels
HTN, Wt gain, truncal obesity, moon facies, buffalo hump, virilization in women
Cushing Disease
ACTH-secreting pituitary microadenoma
- pituitary form of cushing syndrome
Hyperglycemia; Muscle wasting; Central obesity; Round face, supraclavicular fat, buffalo hump; Osteoporosis; Striae; Virilization and menstrual disorders in women; Hypertension
Cushing Dx treatment
Ketoconazole - an inhibitor of steroid hormone synthesis
or Metyrapone
Conn’s Syndrome
Hyperaldosterone caused by aldosterone secreting tumor
Hypertension; Hypokalemia; Metabolic Alkalosis; Decreased Renin
Tx of Conn’s
Spironolactone (aldosterone antagonist)
17α-Hydroxylase deficiency
↓ adrenal androgens and glucocorticoids; ↑ mineralcorticoids; ↑ ACTH
Lack of pubic and axillary hair in women; hypoglycemia; metabolic alkalosis, hypokalemia, hypertension
21β-Hydroxylase deficiency
↓ glucocorticoids and mineralcorticoid(cortisol and aldosterone); ↑ adrenal androgens
Virilization of women; Early acceleration of linear growth; Early appearance of pubic and axillary hair
Links beta cells and alpha cells in the pancreas
Gap Junctions
Decrease blood glucose stimulates this
Glucagon
Actions of Glucagon
increase glycogenolysis, gluconeogenesis, lipolysis and urea production
decreases phosphofructoskinase activity
Central Islet
beta cells, insulin
outer rim of islet
alpha cells, glucagon
intermixed in islet
delta cells that secrete somatostatin and gastrin
second messenger for glucagon
cAMP, acts of liver and adipose tissue
What to measure in diabetics to see if they’re making insulin
C-peptide
Major factor that stimulate insulin
blood glucose (which binds Glut 2 on beta cells)
Sulfonylurea drugs
tolbutamide and glyburide, stimulate insulin secretion by closing K channels
Insulin receptor
tetramer with 2 alpha and 2 beta subunits.
Beta subunits span the cell membrane and have TK activity
Factors that decrease insulin secretion
decreased blood glucose, somatostatin, NE and epinephrine
Factors that increase insulin secretion
increased blood glucose, AA like arginine, lysine, leucine, increased FA, glucagon, GIP and ACh
of insulin receptors in obesity and starvation
insulin downregulates itself so they will increase in number in starvation and decrease in number in obesity
Insulin and Potassium
insulin decreases K in blood and increases its uptake into cells
Diabetes Mellitus
Insulin Deficiency: Hyperglycemia, Hypotension, Metabolic Acidosis, Hyperkalemia
Positive Calcium Balance
growing children, intestinal Ca absorption exceeds urinary excretion, and excess is deposited in growing bones
Negative Calcium Balance
in women during pregnancy or lactation. intestinal calcium absorption is < calcium excretion
PTH is secreted from where?
Chief cells in parathyroid glands
Secretion stimulus for PTH
decreased serum calcium
Secretion stimulus for Vit D
decreased serum calcium, increased PTH, decreased serum phosphate
Secretion Stimulus for Calcitonin
increased serum calcium
Action of PTH on Bone
increases resorption to increase serum calcium
same as vit D
Action of Calcitonin on Bone
decreases bone resorption
Action of PTH on Kidney
decreases phosphate reabsorption but increasing urinary cAMP
increase calcium reabsorption in DT
Action of Vit D on Kidney
increases phosphate reabsorption
increase calcium reabsorption
Action of PTH on intestine
increases calcium reabsorption
increase calcium absorption by activating vit D
Action of Vit D on Intestine
increases Calcium absorption bu calbindin D-28K) and phosphate absorption
PTH on serum calcium and phosphate
increase in calcium, decrease in phosphate
Vit D on serum calcium and phsophate
increase both phosphate and calcium
calcitonin on serum calcium
decreases serum calcium, puts it back into the bones
Parathyroid adenoma
Most common cause of primary hyperPTH
hypercalcemia, hypoPhos, phosphaturic effect of PTH (increase urine secretion of Phos), increase calcium excretion by increase filtered load of Calcium, increase urinary cAMP, increase bone resorption
Humoral hyperCa of Malignancy
PTH-related peptide from malignant tumor, increase bone resorption, hyperCa, hypoPhos, decreased serum PTH due to increase serum Calcium
Most common cause of Hypoparathyroidism
Thyroid surgery
HypoPTH
hypocalcemia (tetany)
hyperPhos
Albright’s Hereditary Osteodystrophy
PseudohypoPTH type Ia
defective Gs protein in kidney and bone causing end organ resistance to PTH
hypocalcemia and hyperphosphatemia can’t be corrected with exogenous PTH
PTH elevated
Chronic Renal Failure
decreased GFR, increase serum phosphate, decrease calcium
decreased production of 1,25-dihydroxycholecalciferol
secondary hyperPTH
Renal osteodystrophy
S/E of chronic renal failure, increased bone resorption and osteomalacia
Vit D deficiency in kids
Rickets
Vit D deficiency in adults
Osteomalacia
Active form of Vit D
1,25-dihydroxycholecalciferol which made in kidney from 1alpha-hydroxylase
1alpha-hydroxylase activity is increased when
decreased serum calcium, increased PTH, decreased serum phosphate
Secreted by Parafollicular cells of the thyroid
Calcitonin, inhibits bone resorption, used to treat hyperCa
genetic sex
XX is female
XY is male
Gonadal sex
testes in males
ovaries in females
Phenotypic Sex
characteristics of internal genital tract and the external genitalia
testes secrete
Antimullerian hormone and testosterone
Sertoli Cells
secrete antimullerian hormone
FSH acts on this to maintain spermatogenesis
Produces inhibin
Leydig cells
stim cholesterol desmolase
LH acts on this to promote testosterone synthesis
Mullerian Ducts
Female internal genital tract
5alpha-reductase
In prostate, converts testosterone to its active form dihydrotestosterone
Finasteride
5alpha-reductase inhibitor used to tx benign prostatic hyperplasia
Arcute nuclei of hypothalamus
secrete GnRH
Inhibin
produced by Sertoli Cells to inhibit the secretion of FSH
Cause pubertal growth spurt and cessation of it (epiphyseal closure)
Testosterone
Paracrine effect of Spermatogenesis in Sertoli cells
Testosterone
Deepens Voice
Testosterone
Causes differentiation of penis, scrotum, and prostate
Dihydrotestosterone
Male hair pattern and male pattern baldness
Dihydrotestosterone
Growth of Prostate and sebaceous gland activity
Dihydrotestosterone
Androgen Insensitivity Disorder
testicular feminizing syndrome
deficiency of androgen receptors but increased testosterone
femal external genitalia and no internal geital tract
Childhood LH and FSH
low but FSH>LH
cause you eat more goldfish in childhood
Puberty and Reproductive Years LH and FSH
hormone levels are increased and LH > FSH
Senescence LH and FSH
hormone levels are the highest FSH > LH
Theca Cells
produce testosterone in females (stim at 1st step by LH)
and then diffuses to granulosa cells
LH from theca cells change cholesterol into pregnenolone
Granulosa cells
contain aromatase and convert testosterone to 17beta-estradiol (stim by FSH)
Causes the development of female secondary sex characteristics at puberty
estrogen
Progesterone participates in the development of breasts
Causes proliferation and development of ovarian granulosa cells
Estrogen
Lowers uterine threshold to contractile stimuli during pregnancy
Estrogen
Has negative feedback effects on FSH and LH secretion during luteal phase
Progesterone
Maintains Pregnancy
Estrogen and progesterone
Raises uterine threshold to contractile stimuli during pregnancy
Progesterone
Maintains secretory activity of the uterus during luteal phase
Progesterone
Follicular Phase
days 0-14
primordial follicle becomes graafian w/ atresia of neighboring follicles
estradiol levels increase and proliferate the uterus
FSH and LH are suppressed, progesterone is low
Ovulation
Day 14 if on a 28day cycle
burst of estradiol has + feedback effect on secretion of FSH and LH (LH surge)
cervical mucus increases in quantity, less viscous
Luteal Phase
Days 14-28
corpus luteum develops and synthesizes estrogen and progesterone
basal body temps increase due to progesterone
vascular and secretory activity of endometrium increase
Lack of fertilization
no fertilization in luteal phase will cause corpus lueum to regress and estradiol and progesterone levels decrease abruptly
Menses
days 0-4
endometrium is sloughed due to abrupt withdrawal of estradiol and progesterone
Pregnancy
steadily increasing levels of estrogen and progesterone to maintain the endometrium
inhibit FSH and LH and stimulae breast development
fertilization
corpus luteum is rescued from regression by hCG which is produced by the placenta
1st Trimester
corpus luteum (stim by hCG) is responsible for productino of estradiol and progesterone peak levels of hCG at week 9 gestation
2nd and 3rd Trimester
progesterone from placenta
estrogens from fetal adrenal gland and placenta
Major Placental estrogen
Estriol
Human Placental Lactogen
produced throughout pregnancy, actions similar to GH and prolactin
Parturition
Progesterone increases threshold for uterine contraction
near term, estrogen/progesterone ratio increases making uterus more sensitive to contractile stimuli
Effects of Prolactin
inhibits GnRH secretion, therefore inhibits LH and FSH
antagonizes actions of LH and FSH
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