endocrine terms exam 3 Flashcards
Hypothalamus
Secretes TRH, GnRH, CRH, GHRH
and DA that stimulate or inhibit pituitary gland function/prolactin.
leptin targets here
target of hypothalamus
pituitary glands
where does leptin target
hypothalamus
where is DA released from
hypothalamus
Heart
atrial natriuretic peptide lowers blood Na+.
hormone lowers blood Na+
atrial natriuretic hormone
adrenal medulla
epinephrine and norepinephrine, fight-or-fight response
adrenal cortex
aldosterone: regulates Na+ and K+ balance;
cortisol, androgens
released from anterior pituitary
ACTH, FSH
LH, GH
PRL, TSH
released from hypothalamus
DA, TRH, GnRH, CRH, GHRH
liver
IGF-1 control bone growth
angiotensinogen: precursor of angiotensin II
prods non-specific carrier proteins
hormone controls bone growth
IGF-1 from liver
angiotensinogen
secreted from liver
precursor of angiotensin II
kidneys
secrete erythropoietin - regulates maturation of RBCs
active 1,25 vitamin D
renin: synthesizes angiotensin II
hormone renin
secreted by kidneys
starts synthesis of angiotensin II from precursor of liver, angiotensinogen
pancreas
insulin decreases blood glucose
glucagon increases blood glucose
insulin
decreases blood glucose
hormone decreases blood glucose
insulin from pancreas
hormone increases blood glucose
glucagon from pancreas
hormone glucagon
from pancreas, increases blood glucose
blood vessels
walls finish synthesis of angiotensin II to maintain normal BP
adipose tissue
regulates appetite and metabolism
active form vitamin D
1,25-dihydroxyvitamin D from kidneys
erythropoietin
secreted from kidneys
maturation of RBCs
posterior pituitary gland hormones
oxytocin and vasopressin = antidiuretic hormone
vasopressin
antidiuretic hormone released from posterior pituitary gland with oxytocin
increases water reabsorption in kidneys
increases water reabsorption in kidneys
vasopressin = antidiuretic hormone released from posterior pituitary
oxytocin
released from posterior pituitary
pineal gland
makes melatonin - circadian rhythm
melatonin
from pineal gland
circadian rhythm
melatonin from pineal gland
thyroid
thyroid hormone
calcitonin: Ca2+ homeostasis
calcitonin
from thyroid, role in Ca2+ homeostasis
stomach and small intestine
gastrin
secretin
cholecystokinin
ovaries
estrogens - estradiol and progesterone
derived from AA Tyr
amine hormones
amine hormones
thyroid hormones, catecholamines, dopamine, melatonin
thyroid hormone
iodine-containing
where are adrenal glands
above each kidney
anatomy of adrenal glands
inner adrenal medulla secretes catecholamines
surrounding adrenal cortex secretes steroid hormones
about adrenal medulla
modified sympathetic ganglion without axons and secretes catecholamines but 4x epinephrine > norepinephrine
PNMT
adrenal medulla enzyme
norepinephrine + PNMT = epinephrine
catecholamines
epinephrine, norepinephrine, dopamine
high expression of PNMT converts most of norepinephrine into epinephrine
dopamine
synthesized in hypothalamus
released in portal system to pituitary gland
inhibitory
most hormones are what type?
peptide
synthesis of peptide hormones
- preprohormones on ribosomes
- preprohormone cleaved into prohormone by proteolytic enzymes in rough ER
- PTM: prohormone cleaved into ACTIVE hormone and other chains
- Packaged into vesicles by Golgi
- exocytosis
receptor location for peptide hormones
on plasma membrane
peptides are hydrophilic
statins
inhibit cholesterol production
steroid hormones
derived from cholesterol
ring stucture
lipophilic/hydrophobic so bind intracellular receptors of nuclear receptor family to alter gene expression and change rate of protein synthesis
endogenous cholesterol
mitochondria
what secretes steroid hormones
adrenal cortex and gonads/placenta
vitamin D
can be enzymatically converted in steroid
synthesis of steroid hormone
- cholesterol
- anterior pituitary hormone binds membrane receptor and stimulates synth
- receptors linked to Gs proteins which activate adenylyl cyclase and cAMP
- activated cAMP fires up protein kinase A to phosphorylate proteins
- enzymes convert
diseases of liver
affect carrier proteins and so hormone delivery
affect IGF-1 and bone growth
carrier proteins
steroid proteins use carrier produced in liver like albumin
non-specific and low affinity
5 adrenal cortex hormones
- cortisol = glucocorticoid
- aldosterone = mineralocorticoid
- DHEA = androgen
- androstenedione = androgen
- corticosterone = glucocorticoid
cortisol
from adrenal cortex, glucocorticoid
affects glucose/metabolism
zona fasciculata
aldosterone
mineralocorticoid of adrenal cortex
- effects on salt/ion balance in kidneys to stimulate Na, H20 retention and K+, H+ secretion
- under control of angiotensin II
can be converted from corticosterone in outer glomerulosa layer of cortex
angiotensin II regulates aldosterone
aldosterone of adrenal Cortex
angiotensin II binds membrane of adrenal cortex to activate inositol triphosphate 2nd mess. path
stimulates Na+ and H2O retention and K+, H+ excretion in kidneys
aldosterone of adrenal cortex, regulated by angiotensin II
glucocorticoids
cortisol and corticosterone from adrenal cortex
layers of adrenal cortex
outer: zona glomerulosa has enzymes to synthesize corticosterone and convert it to aldosterone
zona fasciculata
of adrenal cortex produces cortisol
zona reticularis
produces androgens
effects of CAH congenital adrenal hyperplasia
excess androgens in female virile genitalia to look male
cholesterol converts into…
pregnenolone –> DHEA, androstenedione, cortisol
corticosterone –> aldosterone
water soluble, hydrophilic
peptide and catecholamine hormones
- dissolve in plasma
hydrophobic, lipophilic
steroid and thyroid hormones
- bind to carrier proteins produced by liver
small conc. are dissolved in plasma and FREE!!!
rate of excretion for steroids
slow, protein bound,
bind intracellular and alter gene expression, protein synthesis
rate of excretion for thyroid hormone
slow
protein bound and protected from excretion/metabolism
binds intracellular
rate of excretion for peptide and catecholamines
fast
free/unbound and bind membrane receptors
Hormone concentration in blood depends on:
- rate of secretion by gland
- rate of removal from blood
remove by excretion or metabolism with liver and kidneys
protein bound hormones
protected from removal/excretion/metabolism
Hormone activation by metabolism
thyroid gland produces T4 and converted to active T3 in target cell
up-regulation
increase number of receptors in cell after prolonged exposure to low concentrations of hormone will have EFFECT of increased responsiveness of target-cell
increase response of target cell?
up regulation of receptors
increase # receptors with prolonged exposure to low concentrations of homrone
down-regulation
decrease in receptor # after exposure to HIGH CONCentrations decreases target responsiveness to hormone, preventing overstimulation!
prevent overstimulation
down regulate # receptors in cell
after exposure to HIGH concentration of hormone
exposure to high conc. hormone
down-regulate/decrease # receptors to prevent overstimulation
permissiveness
Hormone A must be present 1st for Hormone B to fully work / hormone A enhances hormone B
how does permissiveness work
hormone A up regulates hormone B’s receptors so it can fully work
epinpehrine
stimulates release of fatty acids into blood from adipocytes for energy
NEEDS permissive amounts of thyroid hormone
example of permissiveness
epinephrine releases fatty acids into blood for energy
NEEDS thyroid hormone
- thyroid hormone stimulates synthesis of beta-adrenergic receptors for epinephrine in adipose tissue so it becomes more sensitive to epinephrine
epinephrine receptors
beta-adrenergic on plasma membrane
thyroid hormone stimulates beta-adrenergic receptors on adipose tissue to be more sensitive to epinephrine so it can release fatty acids into blood for energy in permissiveness
Ca2+
second messanger
electrical potential
open/closing ion channels changes potential
inputs that control hormone secretion
- changes in plasma concentrations of ions/nutrients
- NT release from neurons synapsing on endocrine cells
- another hormone or paracrine body
rate of hormone secretion depends on…
relative amounts of stimulator or inhibitory inputs (NTs, hormones, ions)
nitric oxide
vasodilator
Communication by extracellular signals
- synthesis
- release of hormone
- transport to target
- detection by receptor
- receptor-signal complex activates and trigger change
- removal of signal terminates response (removal from blood by excretion or metabolism OR reduced release from gland)
Regulation of Hormone
Concentration
- PRODUCTION RATE - synthesis and secretion (gene expression cascades)
- DELIVERY RATE - blood flow
BINDING/CARRIER proteins in blood increase half life of hormones - Inactivation/elimination rate - intrinsic decay rate, metabolized, excreted, catabolic enzymes
chromaffin cells
respond to ACh by increasing Ca2+ conductance and triggers exocytosis from vesicles
PROGRESSES in POSITIVE + feedback loop
in adrenal medulla, for catecholamines
source of catecholamines
adrenal medulla and postganglionic sympathetic neurons
postganglionic sympathetic neurons
source of catecholamines (in addition to adrenal medulla)
general synthesis of steroid hormones
derived from cholesterol and enzymatic conversions
DHEA –> adrostenedione
corticosterone –> aldosterone
determinant of final steroid hormone product
expression of specific enzymes and concentrations
what does increased secretion of steroid hormones indicate?
increased rate of synthesis
- cholesterol
consequences of liver disease
affects carrier protein production and hormone delivery (steroid and thyroid)
a dietary deficiency in iodine can cause
slow mental functions,
congenital hypothyroidism
low metabolic rate
goiter
when is GH secretion the greatest
adolescence
How does GH stimulate cell proliferation
GH stimulates release of IGF-1 from the liver and other target tissues of GH
patient is irritable and SWEATY. had lump near thyroid. blood plasma has low levels of TSH?
graves disease
what stimulates secretion of GH
exercise
when really stressed, hormones?
increased secretion of ACTH (adrenocorticotropic hormone) from HYPOTHALAMUS
ACTH from hypothalamus/adenohypophysis
during stress, secretion increased ACTH
if adrenal gland’s removed: plasma cortisol ____, secretion of CRH by the ____ would _____, secretion go ACTH by the _____ would ______.
plasma cortisol DECREASES
CRH secreted by HYPOTHALAMUS would INCREASE
ACTH secreted by ADENOHYPOPHYSIS would INCREASE
adrenal gland removal effects on cortisol
plasma cortisol DECREASES
adrenal gland removal effect on CRH
cortisol decrease and ACTH from HYPOTHALAMUS INCREASES
adrenal gland removal effect on ACTH
ACTH secretion INCREASES from hypothalamus/adenohypophysis
cortisol decreases
CRH increases from hypothalamus
precursor of cortisol is
progesterone made from cholesterol
cortisol is secreted by the
adrenal cortex when stimulated by ACTH from ANTERIOR PITUITARY
secreted ACTH?
anterior pituitary secretes adrenocorticotropic hormone to stimulate cortisol synthesis in cortex
actions of ACTH
secreted from anterior pituitary, stimulates synthesis of cortisol from cholesterol/progesterone
EX of long loop negative feedback
Inhibition of GHRH release by IGF-1
median eminence of hypothalamus
site where neurohormones are released into blood vessels that pass directly to anterior pituitary
hormones that influence the secretion of other hormones?
tropic = trophic
TRUE of steroid hormones RECEPTORS
undergo allosteric modulation when bind,
in nucleus
may be proteins
regulate gene transcription
NOT synthesized from cholesterol
where to find steroid receptor
cytoplasm or nucleus
functions of liver
plasma proteins to bind hormones
secretes angiotensinogen
secrete IGF-1
clear hormones from plasma
disease of ribosomes in anterior pituitary affects which hormones ?
GH
characteristic of cells that secrete steroid hormone?
abundant smooth ER and FEW SECRETORY GRANULES
adrenal cortex, gonads/placenta
true of hormones
sometimes secreted by neural tissue
can be local regulators and NTs
secreted by ductless glands
influences/influenced by nervous system
NOT true of endocrine system
NOT anatomically connected
rate limiting step of steroid hormone synthesis
cholesterol transported to inner mitochondria to be converted into pregnenolone = RDS
in the cytoplasm, its converted to progesterone and converted in ER to cortisol
ER for steroid hormone synthesis
smooth ER
where are chromatin cells
adrenal glands or ganglia
release catecholamines
RIA radioimmunoassay
competitive assay to measure hormone levels
ghrelin?
appetite stimulant
secreted by stomach during fasting
acts on HYPOTHALAMUS
works in anticipation of food = highest gherkin before meals
happens during fasting
blood insulin drops and ghrelin INCREASES
ghrelin binds its receptor and stimulates release of GH
ghrelin stimulates?
released from stomach in fasting
stimulates GH from pituitary gland to MOBILIZE E stores and prevent hypoglycemia
ghrelin + correlated with…
GH from pituitary gland to mobilize E stores to prevent HYPOGLYCEMIA
GH + correlated with
GHRELIN from stomach stimulates GH during fasting to mobilize E stores and prevent hypoglycemia
effects of GH during fast
mobilizes E stores by promoting lipolysis of adipose and inhibits glucose uptake to increase blood glucose and prevent hypoglycemia
in liver, GH enhances gluconeogenesis and autophagy
GH on liver
stimulated by ghrelin, enhances gluconeogenesis and autophagy
autophagy
(of liver): TURNOVER
GH induces liver lysosomal degradation and recycling to engulf and catabolize intracellular materials to regenerate new
lipolysis
induced by GH in response to high ghrelin
energy metabolism in adipose releases free fatty acids for energy and preventing hypoglycemia during fasting
gluconeogenesis
hepatic
stimulated by GH in response to ghrelin
LIVER (kidneys): de novo synthesis of glucose from noncarb. precursors to maintain blood glucose and prevent hypoglycemia during fasting
(glucose can be synthesized from lactate, glycerol, AA)
de novo glucose synthesis
haptic liver gluconeogenesis stimulated by GH during fast (high ghrelin) from non-carbohydrate sources
relationship between blood glucose and triglycerides
triglycerides are fat stores of E that liver can use in gluconeogenesis during a fast
when blood glucose FALLS, hepatic triglycerides also DECREASE
GH actions during starve
insulin drops.
ghrelin stimulates GH to act on liver and adipose in lipolysis to release fatty acids, induce hepatic autophagy and gluconeogenesis and prevent hypoglycemia
hepatic triglycerides decrease
primary target of GH
liver receptors
then secondary adipose - lipolysis
leptin
feeling full, suppress hunger
RIA materials
radioactively labeled hormone of interest = LIGAND
unlabeled hormone competitor
Artificial Antibody = RECEPTOR
RIA
competitive assay to determine hormone levels
hormone = ligand
antibody = receptor
Radioactive hormone and unlabeled hormone compete to bind same sites on Abs & bind proportionally to respective concentrations
RIA experiment 1
- test tubes 1-5 have increasing amounts of radioactive hormone
all tubes have same amount of antibody receptors - let hormone (ligands) bind AB receptor and come to EQ
- precipitate and wash Abs
- measure radioactivity and create standard curve of binding
RIA experiment 2
- choose hormone dose and set up test tubes 1-5 with same dose of radioactive hormone and same amount of antibody receptors
- add increasing amounts of unlabeled, competing hormone to each tube
- precipitate and wash ABs to quantify radioactivity vs hormone conc.
determine amount of unknown hormone with decreasing standard curve
secretion
rate depends on stimulatory/inhibtory inputs
= exocytosis from cell
plasma conc of ions/nutrients
influences Hormone Secretion through NEGATIVE = feedback loop
EX: insulin secretion stimulated by high glucose conc.
insulin acts on muscles and adipose to promote uptake/diffusion from blood into cytosol to restore normal blood glucose which decreases insulin
EX: decrease in plasma Ca2+ concentration stimulates PTH secretion to increase Ca2+ release into blood and restore to normal
hormone secretion controlled neuronally
parasympathetic and sympathetic inputs
- adrenal medulla is modified sympathetic ganglion and stimulates by sympathetic preganglionic fibers
hormone secretion controlled by other hormones
Permissiveness: hormone A is necessary for full functional effect of hormone B
(may up-regulate or enhance effect)
Hormone A stimulates secretion of B
Tropic / trophic = stimulates secretion of next hormone
tropic
stimulates secretion of another hormone
where is synthesis of thyroid hormone
follicular epithelial cells and EC colloid
T4
main secretory product = thyroxine
converts into T3
thyroxine
T4 = main secretory product converted into T3
T3
triiodothyronine is main ACTIVE thyroid hormone and has receptors all over body so effects are vast
T4 converts in to T3
triiodothyronine
T3 = main ACTIVE thyroid hormone
follicular epithelial cells
surround colloid, site of thyroid hormone synthesis
colloid
thyroglobulin protein rich core of follicular epithelial cells
stimulation of thyroid hormone production
TRH thyrotropin releasing hormone FROM HYPOTHALAMUS stimulates secretion of TSH from ANTERIOR PITUITARY GLAND
what stimulates thyroid hormone production
TRH from hypothalamus stimulates TSH from anterior pituitary
where is TSH from
anterior pituitary
stimulated by TRH of hypothalamus
general synthesis of thyroid hormone
- TRH from hypothalamus stims TSH of anterior pituitary
- iodide trapping: iodide and Na+ transported across follicular epithelial cells and Na+ pumped back out with pump
- I is transported by PENDRIN into colloid
- in colloid, enzymes oxidize/organifi and attach iodide into iodine-thyroglobulin complex
- ring of 1 complex removed and coupled to another DIT forms T4/T3
- part of colloid w iodinated thyroglobulin is endocytose and hormones released into blood with carrier proteins/transports
require transporter in blood
thyroid hormones and steroids
thyroid adaptation
ability to store iodinated-thyroglobulin in colloid is necessary given the unpredictable intake of iodine in diet
thyroid hormone feedback
thyroid hormones exert NEG - feedback to inhibit anterior pituitary (TSH) and hypothalamus (TRH)
thyroid hormones actions
like steroids, alter gene transcription and protein synthesis
T3 stims carb absorption and fatty acid release from adipose
provides E (fatty acid release w/ epinephrine) to maintain high metabolism
regulates synthesis of GH
T3 stims chondrocyte differentiation and growth new blood vessels
Energy use in thyroid hormone synthesis
E to pump Na/K+ pump
- uses ATP
ATP concentration controlled by - feedback of T3/T4
decrease in ATP releases NEG feedback and triggers increase in glycolysis to restore ATP conc.
permissive action of thyroid hormone
on catecholamines (sympathetic activity)
T3 up regulates beta-adrenergic receptors of epinephrine so more sensitive
- synergistic with epinephrine to stimulate release of fatty acids from adipose
hypothyroidism
iodine deficiency = synthesis T3 compromised
1. decrease in T3 releases NEG - feedback on hypothalamus/anterior pituitary
2. TRH and TSH secretion increase in portal circulation
3. overstimulation of thyroid gland by increased TRH and TSH secretion produces goiters
causes of hyposecretion
enzyme deficiency (iodine)
gland damage
congenital hypothyroidism
T3 absent
loss of negative feedback = increased secretion of TRH and TSH which overstimulate thyroid and produce goiters
Hashimoto’s
autoimmune cells attach thyroid
T3 conc. decreases as thyroid losses function and TRH/TSH increase from loss of NEG - feedback
overstimulation of gland = hypertrophy/goiter
treatment: T4 pill
graves disease
autoimmune - produce antibodies that bind and activate TSH receptors on thyroid = chronic overstimulation of gland
Cushing’s disease
excess glucocorticoids (cortisol) even in non-stress may be ACTH secreting tumor of anterior pituitary
high cortisol conc. promotes uncontrolled catabolism of bone
high cortisol conc. effects
uncontrolled catabolism of bone
pituitary gland
hypophysis
below hypothalamus and connected by infundibulum
hypophysis
pituitary gland
infundibulum
pituitary stalk connects hypophysis/pituitary gland to hypothalamus
median eminence
Junction ~ hypothalamus and infundibulum
capillaries of median eminence form the hypothalamo-hypophyseal portal and allow blood to be directly delivered from ME to anterior pituitary
portal
veins/vessels that connect ~ capillaries
portal vessels drain into capillaries of anterior pituitary
allow blood to be delivered directly from ME to anterior pituitary
adenohypophysis
anterior pituitary arose embryonically
posterior pituitary gland origin
extension of hypothalamus
AXONS of hypothalamus terminate on posterior pituitary capillaries
axons of hypothalamus
terminate on capillaries of posterior pituitary
posterior pituitary hormones
peptides: oxytocin and vasopressin
oxytocin from?
posterior pituitary
vasopressin from?
posterior pituitary
vasopressin action
ADH acts on smooth muscle of blood vessels to cause their contraction which constricts and INCREASES BP
in kidneys:
decrease excretion to retain fluid and maintain blood volume
increase BP?
ADH = vasopressin constricts blood vessels by contracting smooth muscle cells
diuresis
increase in water excreted in urine
hypophysiotropic hormones
produced in hypothalamus, regulate secretion of anterior pituitary
neuronal secretions terminate on median eminence around capillaries
APs cause nuerons to exocytose hormones
hypophysiotropic hormones
produced by hypothalamus
control secretion of anterior pituitary
hypothalamus axons terminate in median eminence around capillaries
WORK in 3-hormone SEQUENCE
hypothalamic vs hypophysiotropic hormones
hypophysiotropic = produced by hypothalamus NEURONS and axons terminate in median eminence around capillaries to control secretions of anterior pituitary
hypothalamic: enter median eminence capillaries and are carried by portal vessels to anterior pituitary gland
hypothalamic hormones
enter median eminence capillaries and are carried by portal vessels to anterior pituitary
ACT in HIGH CONC.
little blood flow in portal veins allows little hormone to control anterior pituitary and prevent unintended effects
hypophysiotropic 3 hormone sequence
DA is exception
1. hypophysiotropic hormone controls excretion of anterior pituitary hormone which controls secretion of
2. hormone from some other gland that acts on target cells
hypothalamic hormones
enter median eminence capillaries and are carried by portal vessels to regulate anterior pituitary secretions
ACT in high conc bc low blood in portal veins which prevents unintended effects
hypothalamic vs hypophysiotropic hormones
hypothalamic - carried in portal vessels to anterior pituitary, act in high conc.
bind to membrane receptors
hypophysiotropic - neuronal, terminate in median eminence around capillaries
hypophysiotropic 3 hormone sequence
- hypophysiotropic hormone controls secretion of
- anterior pituitary hormone which controls secretion of
- other endocrine gland hormone that acts on target cell
value of hypophysiotropic 3 hormone sequence
- feedback
- amplification into large peripheral hormonal signal
6 anterior pituitary hormones
gonadotropic: FSH and LH
GH = somatotropin
TSH = thyrotropin
Prolactin
ACTH = adrenocorticotropic
gonadotropins
FSH and LH by anterior pituitary stimulate the gonads
somatotropin
Growth hormone GH
GH other name
somatotropin, from anterior pituitary
TSH other name
thyrotropin, from anterior pituitary
thyrotropin
TSH, from anterior pituitary
FSH and LH roles
secreted by anterior pituitary onto gonads
GH roles = somatotropin
secreted from anterior pituitary onto LIVER and other
LIVER secretes IGF-1
stimulates IGF-1 secretion
anterior pituitary releases GH (somatotropin) to act on LIVER to secrete IGF-1
GH somatropin target
LIVER
secretes IGF-1
and metabolism
TSH role
anterior pituitary releases TSH onto THYROID
to stimulate T3/T4
prolactin
from anterior pituitary acts on breasts
during lactation, inhibits gonadotropin secretion
ACTH role
secreted from anterior pituitary onto ADRENAL CORTEX to secrete CORTISOL
target of ACTH
adrenal cortex to release cortisol
stimulus for cortisol
ACTH from anterior pituitary onto adrenal CORTEX
ACTH stimulus
CRH = corticotropin RH in hypothalamus stimulates ACTH from anterior pituitary
stimulus for GH release
GHRH in hypothalamus stimulates secretion of GH (SST) from anterior pituitary
stimulus for TSH thyrotropin
TRH thyrotropin RH in hypothalamus stimulates anterior pituitary to release TSH and then thyroid produces T3/4
GnRH
of hypothalamus, stimulate secretion of gonadotropins FSH and LH
2 inhibitory hypophysiotropic hormones
- somatostatin SST INHIBITS GH
- DA inhibits secretion of prolactin
inhibits GH?
SST inhibitory hypophysiotropic
inhibits prolactin
DA hypophysiotropic
Double control of GH
- Inhibitory: SST
- Stimulatory: GHRH
SST
hypophysiotropic hormone inhibits GH on anterior pituitary
neural control of hypophysiotropic hormones
- CNS inputs and neural pathways
- NTs (catecholamines and serotonin) synapse on neurons
- drugs
- circadian rhythm
GH conc. depends on
relative amounts of SST and GHRH
influence on CRH
circadian influence on CRH – ACTH – cortisol
hormonal feedback control of hypothalamus and anterior pituitary gland
NEGATIVE feedback reduces secretions
- EX: neg. feedback on CRH – ACTH –cortisol as cortisol rises
LONG LOOP NEG FEEDBACK
long loop negative feedback
EX: cortisol on CRH, ACTH
3rd endocrine hormone secreted exerts - feedback over anterior pituitary or hypothalamus
3rd endocrine hormone exerts neg. feedback on anterior pituitary/hypothalamus
long loop negative feedback
- controls hypophysiotropic hormones
how does prolactin exert NEG feedback?
short loop negative feedback
prolactin acts on hypothalamus to secrete DA to inhibit prolactin secretion
long loop neg feedback EX
cortisol on ACTH, CRH
short loop negative feedback
influence of anterior pituitary hormone ON HYPOTHALAMUS
EX: prolactin stimulates DA release to inhibit prolactin
controls on thyroid hormone
TRH stimulates TSH stimulates follicular epithelial cells
T3/4 exert negative feedback on anterior pituitary
TSH stimulates…
T3/4 thyroid production
- increase protein synthesis in follicular epithelial cells
- inc. DNA rep and cell division and rough ER machinery
overexposure of / HIGH TSH conc.
hypertrophy of thyroid - goiters
thyroid hormone for temperature homeostasis
Na/K+ pump uses up ATP stores
induce glycolysis to make more ATP
glycolysis has HEAT by-product
heat plays into temp homeostasis of body
different stimuli for ACTH of anterior pituitary
- CRH from hypothalamus
- Vasopressin - Hypothalamus/POSTERIOR pituitary
- cytokines
permissiveness of CORTISOL
with epinephrine/norepineprhine
on blood vessels smooth muscle cells
cortisol helps maintain BP
low cortisol
low BP
(permissive with epi/norepinephrine on smooth muscle cells of blood vessels
overreactive immune system
systemic actions of cortisol
help maintain BP
anti-inflammatory, anti-immune
- cortisol inhibits production of inflammatory bodies and suppresses growth of lymphocytes
= brake on immune system to prevent overreactions to minor infections in absence of cortisol
- fetal tissue differentiation
cortisol and stress
- mobilize E sources
- catabolism liberates AAs for hepatic gluconeogenesis and tissue repair
- enhances sensitivity and contractibility/vasoconstriction of vascular smooth muscle in response to norepinephrine
- suppress potentially damaging inflammation
- suppress non essential functions
chronic stress
loss of muscle tone, compromised immune system is vulnerable, delayed puberty/suppressed growth/low fertility
low BP and low glucose patients
adrenal insufficiency
need cortisol permissiveness with epinephrine
hypothalamus project axons
- to median eminence: hypophysiotrophic hormones circulate to anterior pituitary to secrete tropic hormones of EPITHELIAL ORIGIN
- to posterior pituitary
anterior pituitary hormone origin
EPITHELIAL origin
tropic hormones
hypophysiotropic hormone origin
hypothalamus - NEURONAL
requirements for thyroid hormone production
iodine
TRH fast facts
tripeptide synthesized in paraventricular nucleus in hypothalamus
binds Gq receptor on pituitary thyrotopes
- median eminence portal circulation
- stimulates TSH glycoprotein
TSH fast facts
glycoprotein with alpha and beta subunit
thyroid hormone critical functions
- permissive in sensitizing tissues to epinephrine for fatty acids lipolysis and E
- accelerate metabolism
- influence growth and development - SYNERGIZE w GH
colloid
acellular
produces thyroid hormones produced
lining around is acinar cells: secrete into colloid and endocytose to release hormone
concentrate iodine into colloid
follicular epithelial cells
acinar cells
TSH receptor
lining of colloid;
endocytose to release hormones
TSH receptor
on thyroid = acinar cell lining of colloid
receptor is GPCR that activates/couples Gq and Gs pathways
TSH functions on thyroid
stimulate release of hormones from follicular epithelial cells
- increase exocytosis of thyroglobulin from colloid to be released
graves disease auto-antibodies
mimic TSH and overstimulate thyroid
thyroid hormone delivery/transport
T4 much higher concentration and locally converted to T3 at target
T3 lower concentration
- Bound to TBG (thyroxine binding globulin) and albumin
- binds RxR receptor in cytoplasm to translocate into nucleus for genomic effects
thyroid hormone receptor
RxR receptor in cytoplasm allows TH to translocate into nucleus for genomic effects
RxR receptor
for thyroid hormone
in cytoplasm, allows translocation into nucleus for genomic effects
T3 gene regulation
T3-RxR receptor complex can bind a DNA element and do histone acetylation so chromatin opens up
- activate fatty acid synthetase
- negative feedback is genomic!!!
CRH-ACTH pathway
- CRH produced in hypothalamus (or cytokines or Vasopressin)
- portal circulation
- anterior pituitary secretes ACTH
- ACTH circulates systemically to target adrenal cortex
- increase cortisol synthesis - steroid
maintains BP, permissive to epinephrine/norepi.
mobilize E stores
glucocorticoid: release AA and fatty acids, increase glucose w hepatic gluconeogenesis. brakes inflammation. muscle catabolism
multiple levels of negative feedback on hypothalamus or anterior pituitary = short/long loops
cortisol regulation
- negative feedback
ACTH released from anterior pituitary corticotrophs
binds G-coupled receptor on adrenal cortex stimulates adenylyl cyclase
long term activation = up-regulates enzymes required for its synthesis like P450 enzymes and LDL receptors to take in cholesterol
regulation of GH
exercise, stress, fasting, low glucose, sleep
released by anterior pituitary
stimulates LIVER to release IGF-1 & + stimulate hypothalamus to secrete SST which inhibits anterior pituitary & GH inhibits hypothalamus from secreting GHRH
more facts on GH
released in bursts
NOT constitutive
stims LIver to secrete IGF1
Adipose: increase lipolysis (please FAs), dec. glucose uptake
Liver: gluconeogenesis, inc. IGF1
Muscle - decrease glucose uptake, increase protein synthesis = anabolic
chondrocytes: EC matrix and stimulate growth
plasma GH graphs show most release…
in deep sleep, stimulates GH release
IGF-1 system
released from liver by GH
- multiple binding proteins that modulate their activity
- similar effects as insulin
anabolic, lower glucose growth, proliferation
work in higher range
AKT-TOR pathway
anabolic; synthesis
in IGF-1 pathway
IGF-1 pathway
AKT-TOR is anabolic; synthesis
promotes proliferation
IGF-1 acts through P13-kinase to activate AKT and induce anabolic state
- FOXO inhibited by AKT activity
- FOXO promotes catabolism
IGF-2 similar to …
insulin but need higher conc.
lower glucose, anabolic, proliferation, growth
IGF-1 effects on skeletal muscle
IGF-1 over expression express AKT and = muscle hypertrophy
- inhibits FOXO
active FOXO = atrophy
FOXO
promotes catabolism
inhibited by AKT activity
AKT-TOR anabolic state stimulated by P13-kinase
IGF-1 longevity
loss of IGF-1 receptor = increased lifespan (metabolism and anabolic)
activated of FOXO = increased lifespan (turnover of protein)
major hormones influencing growth
- GH - differentiation, stim liver to secrete IGF-1, protein synthesis
- insulin
- TH - permissive for GH
- Androgens
- Cortisol - inhibits growth, stimulates catabolism
gigantism
before puberty
excess GH
super tall, enlarged features
acromegaly
adulthood
enlarged hands, feet, and facial features
excess GH
Hormones that favor bone formation and Increased bone mass
insulin
IGF-1
Androgens
Calcitonin
Hormones that factor decreased bone mass
Parathyroid hormone
cortisol
T3 thyroid
endocrine case study of increased IGF-1
- GH secreting anterior pituitary hormone
- increase in GH conc.
- has anti-insulin effects - increase liver secretion of IGF-1
IGF-1 promotes growth leading to gigantism, acromegaly
IGF-1 can inhibit GHRH in hypothalamus
can stimulate SST in hypothalamus to inhibit GH
can inhibit anterior pituitary release of GH
other hormones released during stress
- insulin DEC.
(insulin stimulates uptake of glucose into adipose) - vasopressin and aldosterone: retain water and Na+
- increase hepatic gluconeogenesis
inc. lipolysis by epinephrine and TH
vasopressin effect
increase renal water (and Na+) retention
antidiuresis
- from posterior pituitary
vaso dilator constricts blood vessels and maintain BP and blood volume
aldosterone during stress
ion balance
retain Na+
insulin during stress
decreases
insulin stimulates uptake of glucose by adipose
opp of lipolysis
norepinephrine in stress
from sympathetic neurons
increase heart rate and respiration
BONE GROWTH
bone is metabolically active of protein collagen and calcium and phosphates
divided into epiphysis and shaft
epiphysis
end of bone, connects to joint
epiphyseal growth plate
actively proliferating cartilage (connective tissue of collagen/proteins) convert cartilage into bone
convert cartilage into bone
epiphyseal growth plate
osteoblasts
bone forming cells at shaft/epiphyseal growth plate
convert cartilage to bone
bone forming cells
osteoblasts
convert cartilage to bon eat epiphyseal growth plate
chondrocytes
lay down new cartilage in interior of plate
lay down new cartilage in interior of growth plate
chondrocytes
cartilage formation
epiphyseal closure
epiphyseal growth plate eventually converts into bone
GH effects on bone
stims cell division in target
promotes bone growth, stims cell division of chondrocytes
GH and muscle
GH stimulates protein synthesis
anabolic, AA uptake and synthesis
GH metabolic effects
lipolysis releases FAs into blood from adipose
stimulates hepatic gluconeogenesis
inhibits insulin from decreasing blood glucose (anti-insulin)
why does fasting, exercise, stress stimulate GH
need increased energy available
Ca2+ homeostasis
depends on kidneys, GI, and bone
osteoid
collagen matrix of bone
osteocytes
osteoblasts when calcified matrix
- cells in mature bone
form TJs
mature, calcified osteoblasts
osteocytes
form TJs
osteoclasts
large multinucleate cells that catabolize/reabsorb formed bone by secreting H ions which dissolve crystals, and enzymes which digest Osteoid
reabsorb old bone and then osteoblasts move in and lay new matrix, which becomes mineralized into osteocytes
large multinucleate cells that reabsorb bone so osteoblasts can lay a new matrix
osteoclasts = catabolize bone
1,25-dihydrozyvitamin D and Ca2+
steroid, active hormone
kidneys
STIMULATES intestinal reabsorption of Ca2+
posterior vs anterior pituitary origin of hormones
anterior pituitary secretes tropic hormones of EPITHELIAL OG
posterior pituitary - supraoptic and paraventricular nuclei synapse = NEURONAL
3 hypophysiotropic hormones on anterior pituitary tropic hormones
- CRH – ACTH – cortisol
- TRH – TSH – Thyroid
- GHRH – GH – IGF-1
sex hormones and bone growth
stimulate bone growth and ultimately stop pit with epiphyseal closure
androgens anabolic
rickets and osteomalacia
kids; adults
deficient mineralization of bone causing soft, fragile bones = bowlegged from weak legs
CAUSED: deficient vitamin D
disease of deficient vitamin D
rickets or osteomalacia
weak bones, soft
osteoporosis
bone matrix and minerals are lost
imbalance of reabsorption and formation
CAUSE: excessive reabsorption by thyroid, cortisol, parathyroid
OR deficient bone formation (insulin, IGF-1, calcitonin, androgens)
benign tumor
adenoma
EX cause of hypertrophy
GH and IGF-1
predict conc of GHRH and SST in portal blood in person w loss of anterior pituitary function (somatotroph)
HIGH GH and IGF-1 without any negative feedback
hypertrophy
DA controls anterior pituitary hormone
prolactin
DA is amine derived of hypothalamus
epinephrine is permissive with
T3 and cortisol
SST released from
digestive organs like pancreas to inhibit GH from hypothalamus/anterior pituitary
hormone conceptual: INCREASE hormone on endocrine cell
increase stimulus = secretes more hormone so conc. hormone increases immediately
increase in hormone secretion also increases more negative - feedback
steady state: return to normal thru NEG feedback
conceptual: inhibit stimulus for hormone secretion
less secretion of hormone = less effect and less NEF feedback
IMMEDIATE: decrease hormone conc.
in absence of neg. feedback, hormone secretion increases
STEADY STATE: return to normal
conceptual: DEC. # hormone receptors
less receptors = less effect of hormone
less effect = less NEG feedback so hormone secretion INC.
STEADY STATE: hormone conc. increases in absence of neg. feedback
conceptual: endocrine cell response to EFFECT if facilitated (enhanced)
enhanced effect = more negative feedback
STEADY STATE: decrease hormone conc. w more neg. feedback from enhanced effect
conceptual: INCREASE carrier protein conc. / synthesis by liver
more hormone is bound in complex, effectively inactive, effectively reduced effect = less negative feedback
less negative feedback from bound hormones that cannot be active induces INC in hormone secretion/conc.
