Flashcards in First Pass Miss Exam 3 Deck (76):
What other hormone do chromophobes release?
What releasing hormones does the arcuate nucleus control?
acidophil releasing hormones (GHRH, PIH = dopamin)+ basophils gonadotrophs only
What releasing hormones does the paraventricular nucleus release?
all the rest: CRH and TRH
What type of receptor is the oxytocin receptor?
GalphaQ -> increases calcium concentrations for duct contraction
What are the three components of the efferent end of the sucking reflex?
1. Inhibit dopamine release to increase prolactin
2;. Stimulation production and release of oxytocin by posterior pituitary
3. Inhibition of GnRH release, preventing further pregnancy
What are the two types of vasopressin receptors?
V1a - Galphaq to increase calcium for vasoconstriction
V2 - in kidney collecting duct increase cAMP to move aquaporin-2 to the membrane
Why doesn't desmopressin significantly raise blood pressure while increasing blood volume?
Does not bind V1a receptor for vasoconstriction
What is TBG?
Thyroxin binding globulin - carries both T3/T4, but has 3x the affinity for T4
What causes Graves' disease?
Antibodies overstimulate follicular cells "thyroid stimulating IGs" - activate TSHR
Goiter can result from increased iodine requirement
What cells produce parathyroid hormone and what type of hormone is it?
Peptide hormone produced via chief cells
What are the short and longterm effects of parathyroid hormone?
Short - stimulate bone deposition by osteoblasts (good osteoporosis treatment)
Long - stimulate osteoblasts to secrete M-CSF, IL-6, and RANK-L to recruit osteoclasts
How does osteoprotegrin work?
It's a decoy receptor for RANK-L, thus preventing some osteoclast recruitment.
How does the PTH receptor work?
High extracellular calcium stimulates GalphaQ to increase intracellular calcium concentration, which actually BLOCKS PTH secretion.
What is the function of PTH in kidney outside of excretion of phosphate + reabsorption of calcium?
Activates 1alpha-hydroxylase enzyme so that 25-OH-D3 (primary circulating form of D3, made in liver) can be converted to 1,25-OH-D3 = Calcitriol.
What are the two effects of calcitriol?
1. Primary effect - increase number of calcium channel + gut resorption of calcium
2. Secondary effect - increase bone breakdown to increase plasma calcium concentration.
Primary effect trumps the secondary effect -> bone will end up being net built.
What stimulates calcitonin secretion?
Primarily GI hormones -> control of blood calcium after a meal, but also high blood calcium in general.
Synthesized as procalcitonin before being cleaved.
What is the function of calcitonin?
Inhibits osteoclasts, decreasing both phosphate and Ca+2. It's super important during pregnancy when cortisol is high and bone tends to be resorbed, prevents bone breakdown.
What causes Rickets?
Vitamin D deficiency in children -> bowed legs due to less mineralization
What causes osteomalacia?
Vitamin D deficiency in adults -> bone weakness and fracture susceptibility
What is the main risk factor for osteoporosis?
Menopause, since estrogen stimulates bone mineralization.
What releases somatostatin? What is its effect?
Periventricular nucleus -> GalphaI to decrease cAMP and prevent GH release from somatotrophs, the most numerous cell type in the gland. Also inhibits TSH release from thyrotropes
Stimulated by IGF-1
Where is GHRH released and what is its effect?
Arcuate nucleus -> GalphaS to increase cAMP and stimulate GH release
Inhibited by IGF-1
When is GH released?
Diurnal pattern -> largest peak 1 hour after onset of sleep, in Stage 3 deep sleep
What stimulates GH release?
Since it has some prodiabetic effects, it is released in response to energy deficiency: hypoglycemia, fasting, exercise, low concentration of FFA, elevated glucagon.
Also: Elevated sex hormones + ingestion of protein rich meal
What suppresses GH release?
GH, IGF-1, cortisol (as in psychosocial short stature), HYPERGLYCEMIA (since it has pro-diabetic effects)
What type of receptor is the growth hormone receptor?
JAK/STAT = janus kinase, induces signal transducer and activation of transcription.
In the receptor tyrosine kinase family
What are the acute effects of growth hormone?
prodiabetic - gluconeogenesis, lipolysis, decreased glucose uptake in muscle
What are the longterm / chronic effects of growth hormone
IGF-1 -> increases macromolecule synthesis, organ size, bone growth, and anabolic effects in general
What hormone is oxytocin related to?
7/9 of the same amino acids as vasopressin
What family is somatotropin in?
Same family as human prolactin
What is the function of IGF-binding proteins?
Prolong the half life of IGF-1 (however, it is a peptide hormone), but limits the activity of the hormone when bound
What type of receptor is the IGF-1 receptor?
Like insulin, heterotetramer with two alpha and two beta subunits, RTK activity
When are IGF-1 levels highest?
Low at birth, and peak during puberty, earlier for females than males
What is Laron syndrome?
A mutation in the GH receptor which accounts for 1/3 of all dwarfism (GH insensitivity)
What enzyme is required for synthesis of cortisol which is not found in the zona glomerulosa?
What enzyme is found in the zona reticularis which forms androgens?
17,20 desmolase, cleaves the side chain to DHEA, which is 19 carbons instead of 21 like pregnenolone.
When is ACTH released?
In a pulsatile fashion, more in the morning and hardly at all at night. Explains highest cortisol in the morning (but broader peaks)
What does elevated ACTH stimulate?
Peptide hormone signalling thru GalphaS - SCC enzyme activation, cholesterol uptake via LDL receptors, and cholesterol ester hydrolysis
What is the function of glucocorticoid and how does it work?
Binds via glucocorticoid receptor.
Increases blood glucose levels -> prodiabetic effect like growth hormone
Connective tissue can be destroyed for gluconeogenic substrates, increases lipolysis in peripheral adipose stores, except in face and trunk where it increases fat deposition (Cushing's symptoms)
What is cortisol's role in inflammation?
It has a role in the entire process, but high levels favor the resolving / lowering of inflammation like corticosteroids in general. This inhibits prostaglandin synthesis via inhibition of phospholipase A2.
What is the overall effect of cortisol?
Insulin antagonist -> takes more insulin to achieve the same effect with cortisol present
What triggers aldosterone release?
1. Increased plasma potassium
2. Angiotensin II
3. Slightly ACTH
Why does cortisol not trip the aldosterone receptor?
Converted to cortisone via the 11-beta-hydroxysteroid-DH-2 (HSD2)
What is ACTH's effect on catecholamines?
Increases E/NE production, but not release, by activating two key hydroxylase enzymes in chromaffin cells.
What is the action of cortisol on the adrenal medulla?
Stimulates the conversion of NE to E via phenylethanolamine N-methyltransferase (PNMT)
Where are E / NE made / stored?
Tyrosine -> dopamine occurs in cytoplasm.
Dopamine -> norepinephrine in chromaffin granule
NE -> E in cytoplasm.
E and NE stored in chromaffin granules at 3:1 ratio
What is the function of CREB?
protein in liver which is phosphorylated by epinephrine's PKA, upregulates gluconeogenic substrates
What are the breakdown products of catecholamines?
metanephrine, normetanephrine, VMA
What can cause Cushing's syndrome?
glucocorticoid excess for inflammatory disorder treatment
How do Cushing's disease and Addison's disease affect blood pressure and potassium concentrations?
Cushing's: ACTH excess - slight overproduction of aldosterone -> hypertension + hypokalemia
Addison's: ACTH deficiency - slight underproduction of aldosterone -> hypotension + hyperkalemia
How does the Atk (PKB) pathway for insulin receptor action work?
Ras-independent -> IRS phosphorylates PI-3-K, signals PIP3 to activate Akt. Akt will phosphorylate glycogen synthase kinase, which will inactivate it and prevent phosphorylation of glycogen synthase which would deactivate it.
AKT also modulates migration of GLUT4 to cell membrane
What is one important effect of insulin in muscle for athletes?
Increases lipogenesis, allowing for long-term energy storage
What are the effects of insulin on adipose tissue?
increase GLUT4 transporter for making of glycerol backbone. Increase capillary LPL activity, decrease hormone sensitive lipase (HSL) activity which would normally break down fats.
What is the function of kisspeptin?
Stimulates GnRH release in hypothalamus, upregulated by leptin
How do you remember the pulsatile frequency as it relates to FSH / LH?
Lower frequency = FSH, higher frequency = LH because we know the frequency increases prior to ovulation. Females lose GnRH release at menopause.
When is LH / testosterone often secreted?
During REM sleep, thus, sleep is important for teenage development
What are the relative FSH / LH levels throughout life?
First 1-2 years, increased FSH/LH for early sexual development, then they remain low until puberty. The frequency is constant for males, but females will lose FSH/LH around menopause.
What form of estrogen is in pre-puberty vs puberty?
Pre-puberty: Estrone (E1)
Puberty: Estradiol (E2)
E2 levels are correlated with Tanner stages + bone age in girls
What is McCUne-ALbright Syndrome?
An incomplete, peripheral precocious puberty condition due to a mutation causing constitutive activation of GalphaS receptor, leading to increased E2 or T secretion. Causes a clinical TRIAD:
-Bony fibrous dysplasia
What is pubarche?
Appearance of pubic hair, as a result of adrenarche
What is an example of a hypergonadotropic disorder?
Elevated GnRH levels due to primary gonadal failure, as in gonadal dygenesis of Turner syndrome (deletion or rearrangement of X chromosome).
What is the function of 5-alpha reductase?
Converts testosterone to dihydrotestosterone which is more active, also prevents T aromatization to E2.
What are the consequences of 5alpha reductase deficiency?
Kindreds raised as women because of reduced DHT, they undergo normal development in puberty with large LH spikes due to less negative feedback.
What are the two types of 5-alpha reductase?
Type 1: Skin / scalp
Type 2: Genital skin, prostate, other genital tissues
What gland releases the HCO3' buffer for the vagina in the semen?
Bulbourethral - Cowper's glands + prostate
What releases the enzymes which clot and lequify the semen?
What releases the bulk of the nutrients as well as prostaglandins for smooth muscle contraction in semen?
What are the functions of estrogen in males? What can cause this to be lost?
Epiphyseal fusion, resorption of fluid in the epididymus, energy / metabolic control, upregulation of dopamine + maintanence of smooth muscle.
Aromatase deficiency can cause this to be lost. It is found normally in fat cells.
What is prostate specific antigen?
An androgen receptor target, the anticlotting enzyme of semen
What is the difference between androgen binding protein and sex hormone binding globulin?
Androgen binding protein - used by Sertoli cells to keep T concentrations high in the lumen
Sex hormone binding globulin - used along with albumin to carry sex hormones in the blood, like T and E2
What is the function of estrogen in causing the LH surge?
Increases the sensitivity of the gonadotrophs to GnRH stimulation. By late follicular phase, enough E2 has made them very sensitive to the pulsations in GnRH -> LH SURGE baby
What enzymes are present in theca cells but not granulosa cells?
Enzymes to make androgens (they are like Leydig cells): 17a hydroxylase + 17,20 desmolase
What enzymes are present in granulosa cells but not theca cells?
Aromatase -> they can make estrogens
Both cell types make progesterone, progesterones are transferred to theca cells to become testosterone, testosterone is transferred to become estrogen under FSH stimulation
What enzymes does the placenta lack which are needed to synthesize estriol?
Same ones that granulosa cells lack: 17a hydroxylase + 17/20 desmolase. These functions + 16a hydroxylase are provided by fetal liver + adrenal glands.
What is the maternal function in the maternal-fetal-placental unit?
Takes up cholesterol for hormone production via LDL receptors, and recieves estriol produced in placenta to signal how far along the pregnancy is