protein hormone binds GPCR coupled to adenylate cyclase pathway?
actives g protein which results in activation or inhibition of adenylate cyclase which affects intracellular camp which activates PKA which phosphorylates substrates
where do hormones go from prohormone to hormone
Golgi apparatus packages them and then they are cleaved in vessicles
thyroid hormone receptor activation pathway
thyroid hormone diffuses through membrane and t3 binds TR in nucleus and dimerizes with RXR t4 enters it is deiodinated to t3 dimer binds HRE resulting in gene transcription/ has nongenomic effect as well
Insulin glucagon somatostatin
adrenal medula hormones?
epi and norepi synthesis pathway and storage location
tyrosin to L-dopa to dopamine to norepi to epi synthesized and stored in chromaffin granules
TSH effect on thyoid
1) increases activity of Na/I transporter on basolateral side 2) iodide leaves the cell into the follicular lumen via pendrin channel 3)TSH stimulates iodination of thyroglobulin 4) TSH stimulates conjugation of iodinated tyrosiines linked to thyroglobulin 5)Tsh stimulates endocytosis 6)TSH stimulates proteolosis 7)TSH stimulates secretion of t3 t4 8)stimulates growth factor effect causing hyperplasia of thyroid gland
protein hormone binds GPCR coupled to phospholipase A2 pathway?
Activates G protein which results in activation of PLA2 which cleaves membrane phospholipids to produces lysophospholipid and arachidonic acid. Arachadonic acid is converted into eicosanoids
T3 T4 calcitonin
hormones produced by posterior pituitary?
hormones produced by hypothalamus?
TRH CRH GnRH GHRH somatostatin dopamine
Protein hormone receptors
gpcr, guanylate cyclase, receptor tyrosine kinase
epi release pathwy
preganglionic sympathetics release acetylcholine that causes postganglionic chromaffin cells to depolarize which causes voltage gated ca channels to open exocytosing epi accompanied by atp release
adrenal cortex hormones?
cortisol aldosterone adrenal androgens
where are preprohormones synthesized?
IMPORTANT Thyrotropin releasing hormone (TRH) pathway
TRH bind Activates GPCR which results in activation of PLA2 which cleaves membrane phospholipids to produces lysophospholipid and arachidonic acid. Arachadonic acid is converted into eicosanoids
dopamine synthesis pathway
L-tyrosine -> L-DOPA->Dopamine
beta adrenergic receptor pathways
epi binds beta 1 and 2 along with dopamine DA1 resulting in stimulatory effect activating adenyl cyclase increasing cAMP
endocrine paracrine and autocrine signaling definitions
Endocrine Hormone crosses a large distance to a target tissue Paracrine Hormone crosses an extracellular space to regulate nearby cells Autocrine Hormone binds receptors on or in the cell secreting it
What is the precursor for amine hormones?
all synthesized from tyrosine
what regulates steroid hormones
regulated by trophic hormones from the pituitary
Steroid hormone activation pathway
diffuses through the membrane activates cytoplasmic receptors or nuclear receptors which activate HRE which initiates gene transcription
thyroid hormone sythesis
classified as lipophilic from tyrosine follicular cells secrete iodine and thyroglobulin, iodination of tyrosine molecules on thyroglobulin then conjugation creates t3 and t4 then its endocytosed into folicular cells, proteolysis occurs from thyroglobulin in endolysosome, t3 t4 must be carried by carrier protein
what transporter allows for the uptake of dopamine into chromaffin granules for conversion to epi?
VMAT 1 which can also uptake epi back into chromaffin granule
where are prohormones synthesized?
SER post translational modification
steroid hormone sythesis
from cholesterol LDL in blood or de novo from Acetyl-CoA Cholesterol is converted to the universal precursor, Pregnenolone 20 % from aceteyl coa 80% from LDL
protein hormone binds GPCR coupled to phospholipase C pathway?
gpcr coupled to phospholipase c (PLC) which cleaves PIP2 into IP3 and DAG IP3 releases ER plasma ca stores which activate ca dependent kinases including PKC DAG also activates PKC
hormones produced by anterior pituitary?
TSH LH FSH ACTH MSH GH prolactin
where are the receptors for protein hormones versus steroid hormones and amine hormones?
For protein and amine Hormones the receptors are in the membrane (cell surface) while steroid hormone receptors are inside the cell
what determines which genes are activated by HRE's
specificity of receptors and expression of receptors which is not regulated by the hormone itself
Corpus luteum hormones?
ANP activation pathway
ANP binds guanylyl cyclase increasing intracellular cGMP
Leptin receptor binding and pathway
Leptin binds RTK-> causing phosphylation cascade activating enzymes specifically activates Jak Stat pathway
what is a marker for adrenal medula activity
HCG HPL Estriol progesterone
alpha adrenergic receptor pathways
norepi bind alpha 2 receptor with dopamine DA2= inhibitory effect on adenylly cyclase reducing cAMP levels norepi binds alpha 1= Coupled to Phospholipase C Activates G protein which activats (PLC) that cleaves (PIP2) into (IP3) and DAG IP3 releases endoplasmic reticulum Ca2+ stores, thereby activating Ca2+ dependent kinases, including protein kinase C (PKC).
Thyrotropin releasing hormone (TRH) pathway
Coupled to Phospholipase A2
–Activates G protein which results in activation of PKA2 which cleaves membrane phospholipids to produces lysophospholipid and arachidonic acid.
–Arachadonic acid is converted into eicosanoids
where is the pituitary gland located?
in the sella turcica of the sphenoid bone
what connects the hypothalimus to the pituitary?
a hallow stalk called the infundibulum which is very easily damaged during head trauma
A common complication of a pituitary tumors includes?
compression o fthe optic chiasm resulting in peripheral blindness (tunnel vision)
usually associted with the anterior pituitary and excess GH secretion
Embreological origin of posterior pituitary lobe?
neuroectoderm, part of diencephalon
embreological origin of the anterior pituitary lobe
oral ectoderm, outpouching of the oropharynx
Parts of nuerohypophysis/ posterior lobe of pituitary
Retains histological features of brain tissue
Contains axons of neurons whose cell bodies are in the hypothalamus
Pars nervosa – largest part; contains neurosecretory axons
-Infundibulum – contintuous w/ median eminence; connects pituitary & hypothalamus
-Median eminence - contains hypothalamohypophyseal tracts
Adenohypophysis/ Anterior Lobe of the Pituitary
-Dark- staining epithelial tissue
-Pars distalis – largest part
-Pars intermedia – thin wall separating anterior and posterior lobes
-Pars tuberalis – forms a collar around the infundibulum
What embreological remnant is somteimes seen inside pars intermedia
can contain a remnant of the embryonic hypophyseal pouch (Rathke's puch) and/or colloid-filled cysts
Stimulates liver & other organs to secrete insulin-like growth factor I (IGF-I), which in turn
stimulates division of progenitor cells located in growth plates & skeletal muscles, resulting in body growth
Growth hormone-releasing hormone promotes secretion of GH by the pituitary; Somatostatin inhibits secretion of GH
Promotes mammary gland development; initiates milk formation; stimulates secretion of casein, lactalbumin, lipids, and carbohydrates into the milk
Dopamine inhibits release of prolactin
Stimulates secretion of glucocorticoids & gonadocorticoids by the zona fasciculate & zona reticularis of the adrenal cortex
Corticotrophin-releasing hormone stimulates synthesis of ACTH
Stimulates follicular development in the ovary & spermatogenesis in the testis
Gonadotropin-releasing hormone stimulates secretion of FSH
Regulates final maturation of ovarian follicle, ovulation, & corpus luteum formation; stimulates steroid secretion by follicle and corpus luteum; in males, essential for androgen secretion by the Leydig (interstitial) cells of the testis
Gonadotropin-releasing hormone stimulates secretion of LH
Stimulates growth of thyroid epithelial cells; stimulates production & release of thyroglobulin and thyroid hormones
Thyrotropin-releasing hormone stimulates release of TSH; Somatostatin inhibits secretion of TSH
what do acidophils secrete?
GH & PRL
what do basophils secrete?
ACTH, FSH, LH, & TSH
secrete LH & FSH
in the hypothalumus where do the cell bodies of neurosecretory nuerons reside?
pareventricular nucle secrete what stored where?
secrete oxytocin stored in the posterior pituitary
supraoptic nucle secrete what stored where
secrete adh stored in the posterior pituitary
Oxytocin action and secreted by what
-Oxytocin – promotes contraction of smooth muscle, particularly uterus during labor & myoepithelial cells of the mammary gland during suckling (secreted by paraventricular nucleus)
ADH action stored where
-ADH – (vasopressin) acts on kidneys, regulates water homeostasis and osmolarity of body fluids (secreted by supraoptic nucleus) stored in pars nervosa
Is the posterior pituitary lobe an endocrine gland?
The posterior lobe of the pituitary is not an endocrine gland because it doesn’t synthesize any hormones!
where does the anterior pituitary and infundibulum get its blood suply from?
superior hypophyseal a. - gives rise to the primary capiliary plexus
posterior pituitary blood supply
inferior hypophyseal a. – gives rise to the secondary capillary plexus
The abundant blood supply connecting the pituitary & hypothalamus allows the hypothalamus to regulate cells of the anterior pituitary
How do hypolthalmic hormones reach the posterior pituitary?
Hypothalamic hormones reach the posterior pituitary via neurons;
hypothalamic hormones are stored here.
how do hypothalmic hormones reach the anterior pituitary
hypothalamohypophyseal portal system; hypothalamic hormones
regulate synthesis & secretion of anterior pituitary hormones.
embreological orgin of the adrenal cortex?
-external portion; distinct histological & functional layers; steroid secretion;
originates from mesoderm; 90% of glandular tissue
embreological orgin of adrenal medulla?
-internal portion; secretion of catecholamines (epinephrine & norepinephrine)
originates from neural crest; 10% of glandular tissue
layers of the adrenal cotex from superficial to deep
Zona glomerulosa thin
zona fasciculata thickest layer
what does the zona glomerulosa secrete
Secretion of mineralocorticoids
esp. aldosterone, which regulates salt balance
what does the zona fasiculata secrete?
Secretion of glucorticoids: cortisol & corticosterone; regulation of glucose & fatty acid metabolism
what does the Zona reticularis
Secretion of androgens esp. dehyroepiandosterone (DHEA); secretes very small amounts of glucorticoids
what is the embryological origin of pancreatic islets and acinar cells?
what is the embreological origin of the thyroid
Thyroid gland originates as endoderm from the inferior pharynx. It migrates inferiorly to form the butterfly-shaped thyroid gland
delta cells of the pancreas secrete what?
f cells or pp cells of pancreas secrete what?
parafollicular (c) cells sectete what in thyroid and have what histo characteristics
calcitonin floating not attached to lumen do not contat colloid
what is the emreologic origin of parathyroid glands
Parathyroid glands are derived from the 3rd & 4th pharyngeal pouches (endoderm)
what cells secrete parathyoid hormone?
priciple ceels in parathyroid glands
PTH indirectly stimulates osteoclast activity within bone marrow, in an effort to release more ionic calcium (Ca2+) into the blood to elevate serum calcium (Ca2+) levels.
t acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).
embreological origin of pineal gland and location
part of the diencephalon which is part of the neural tube found posterior to the 3rd ventrical of the brain
pineal gland function
during dark conditions secretes melatonin a tryptophan which is important for regulating circadian rythmes
what are corpora arenacea and where are they found?
-Concretions of calcium & magnesium salts
-Increase in number and size with age
-No understood function or effect on pineal function
found in the pineal gland dark basophilic dots
USE THESE TO IDENTIFY PINEAL GLAND
somatostatin function secreted by
Inhibits secretion of: insulin, glucagon, gastrin, thyroid stimulating hormone, vasoactive intestinal peptide, growth hormone
d cells and hypothalamus
pancreatic polypeptide function
stimulates gastric chief cells/ inhibites bile secretion and intestinal motility and pancreatic enzymes and bicarb secretion
D1 cells (not delta cells) produce what that does what?
VIP which VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder
EC cells of pancreas secrete what
secretin, motulin and substance p, secretin induces bicar secretion and pancreatic enzymnes, motulin gastric motility, substance p is a neurotransmitter
epsilon cells in the pancreas secrete what
ghrelin, stimulates apetite is released with fasting and weight loss
what receptor does insulin bind?
RTK receptor quickly degraded in the plasma by insulinase
insulin release pathway in detail
1.HIGH glucose in blood = glucose moved down its [gradient] into beta cell via GLUT 2 channels via facilitated diffusion
2.Hexokinase (only works at high glucose concentrations) converts glucose into G-6-P to keep the concentration gradient for glucose high = Glucose will be pulled into beta cell as long as plasma glucose is high
3.Beta cells have Na/K pumps and ATP-gated K channels that are open at rest giving beta cells a RMP around -70mV
4.As glucose is brought into beta cell it is converted into ATP = [ATP] in the beta cell rises = closes ATP gated K+ channels = loss of K efflux causes beta cell to depolarize = opens v-gated Ca++ channels. Calcium interacts with snare proteins and secretory granules of insulin and C-peptide are released into bloodstream
5.3-5 minutes after blood glucose levels fall ATP levels fall in the beta cell, ATP gated K+ channels open again, the cell repolarizes, and no more insulin is secreted
glut 1 location and action
RBC's and blod vessels lining the brain, skeletal muscle and fat
basal glucose uptake
expressed by pacreatic betal cells and hepatocytes low affinity allows for uptake only when plasma glucose is high
glut 3 location and function
primarily in neurons together glut 1 and glut 3 allow glucose to cross the blood brain barrier
glut 4 location and function
insulin responsive primarily in striated muscle, fat, remain in vesicals until insulin present moves into membrane
glucagon primary effects and receptor pathway
gpcr activates adenyly cyclase activating PKA, glycogenolysis, gluconeogenesis, fatty acid beta oxydation
What are the effects of insulin on K+ levels in cells?
insulin fascilitaes the entry of K in cells
glp-1 (incretin) does what?
activation leads to increased insulin secretion and inhibition of glucagon secretion... decreased gastric emtying and decreased hunger this response is blunted in t2DM
epinephrin and norepi effect on insulin release
inhibit incretin (glp-1) pathway release of insulin... they help to maintain blood glucose levels
what does DPP-IV do?
it degrades glp-1... drugs that inhibit DPP-IV are used for T2DM treatment
what are the three cuases for obesity induced or t2dm?
–Decreased GLUT-4 uptake of glucose in response to insulin release
–Decreased ability of insulin to repress hepatic glucose production
–Inability of insulin to repress hormone-sensitive lipase (HSL) or increase lipoprotein lipase (LPL) in adipose tissue
a decrease in plasma protein concentration would have what affect on total Ca and plasma Ca concentration
total ca would decrease with protein but plasma ca would stay the same
How does acidemia effect free plasma Ca concentrations?
acidemia leads to increase in ionized ca concentration due to less affinity for albumin not an increase in total ca concentration
how does alkylosis effect free Ca concentrations?
would result in less free ca due to increased binding to albumin no change in total ca levels
numbness in fingertips and extremities,
hyperflexia, overresponive reflexes, muscle twitching, when ca is low sodium channels become HYPEREXCITABLE
decreased action potentials, increased secretion in kidneys
PTH release mechanism
ca binds gpcr coupled to phospholipase C leads to ip3 binding intracellular ca channel which inhibits PTH release from chief cells/ if low ca nothing to inhibit pth release
chronic hyper or hypo calcemia changes to PTH gene transcription
chronic hpercalcemia leads to increase breakdown and decrecreasede sythesis of PTH/ chronic hypocalcemia leads to secondary hyperparathyroidism increased PTH
where is the parathyroid receptor found and action?
osteoblasts causes a brief increase in bone formation but an increase in cytokine release that leads to more osteoclast activity resulting in net bone resorption and increased free ca
also acts on kidney to activate vit D and increase calcium resoprtion by activating ca channels and increaseing number of ca na pumps also blocks phasphate absortion in order to promote free ca/ active form of vit D causes more ca to be absorbed in the gut tube
calcitonin receptor location and function
receptor on osteoclasts it inhibits osteclast activity and is releaesed from thyroid
1-25 dihydroxycholecalciferol (vit d) actions (calcitriol)
increased absorption by the gut tube and increaced bone resorption by acting on osteoblasts to release rankl wich activates osteoclasts
DOES THE OPPOSTITE OF PTH FOR PHOSPHATE nit promotes absorption in kidney
alkaline phosphate is a marker for what?
bione formation/ you will see an increase with pth becasue of osteblast activation
due to severe vit d deficiancy in adults