Hormone Signaling and Synthesis Pathways Flashcards by Matt Stanton

classes of hormones

protein/polypeptides
steroid
amines

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protein hormones

> 100 AA - protein

<100 AA peptide

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release of protein hormones

secretory pathway
-mRNA > RER - preprohormone
-SER - cleaved to prohormone
golgi - packed in vesicle, cleaved to hormone
-exocytosis

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constitutive synthesis

ECM and plasma membrane components

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regulated synthesis

hormones and enzymes

-regulated at level of transcription or exocytosis

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sources of cholesterol for steroid hormones

LDL

acetyl-CoA de novo

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steroid hormones

lipophilic
regulated by trophic hormones from pituitary
-no intracellular stores

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tissues that secrete steroid hormones

adrenal cortex

gonads

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amine hormone synthesis?

from tyrosine

catecholamines and thyroid hormones

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ovaries

estrogen

progesterone

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dopamine synthesis

tyrosine > L-dopa > NE > E

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thyroid hormones

derived from tyrosine
lipophilic** - carried on binding protein

iodination of tyrosine residues on thyroglobulin

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thyroxine

T4 - de-ionated at target tissue

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triiodothyronine

T3 - main effector - higher affinity for receptor

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synthesis of thyroid hormones

trapping:
iodide from blood enters follicular cell through NIS
-TSH increases NIS activity
iodide leaves cell via pendrin to lumen
-thyroglobulin also secreted to lumen

iodination:
iodination of thyroglobulin in lumen
-stimulated by TSH

conjugation:
iodinated tyrosines conjugated to form T4 and T3
-stimulated by TSH

endocytosis:
TSH stimulates endocytosis of iodinated thyroglobulin into follicular cells from lumen (colloid)

proteloysis:
TSH stimulates proteolysis of iodinated thyroglobulin, forming T4 and T3 in lumen of follicular cell lysoendosome

secretion:
TSH stimulates secretion of T4 and T3 into circulation

hyperplasia:
TSH also stimulates growth of thyroid gland

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T/S ratio

ration of follicular cell iodide to plasma iodide

-increases with high TSH**

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affects of TSH

1 increased iodide into follicular cell (trapping)
2 increased iodination of thyroglobulin in lumen
3 increased conjugation of iodinated thyroglobulin to form T3 and T4
4 incrased proteolysis of of iodinated thyroglobulin in lysoendosome
5 increased secretion of T4 and T3 to circulation
6 incrased growth of thyroid gland

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adrenal medullary hormones

E and NE
-catecholamines

synthesized and stored in chromaffin granules

release stimulated by sympathetic innervation
-no negative feedback

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chromaffin cells

synthesis of E and NE in adrenal medulla

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synthesis of medullary hormones

L-tyrosine > L-dopa > dopamine (in cytosol)
dopamine to chromaffin granule (VMAT-1)
dopamine (DBH)> NE (in granule)
NE to cytosol (VMAT-1)
NE (PNMT)> E (cytosol)
exocytosis

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circulating hormones

free or unbound

associated with binding protein

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free or unbound hormones

water-soluble
catecholamines and peptides
short-term and quick acting

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hormones bound to protein

long-term, slow acting

fat-soluble - steroid and thyroid hormones

thyroid hormones binding protein

creates hormone reservoir and extends half life

protein hormone receptors

bind GPCR | -coupled to cAMP, phospholipase C, phospholipase A2

cAMP coupled GPCR

activation (a-s) or inhibition (a-i) of adenylyl cyclase affects cAMP levels cAMP activates protein kinase A

phospholipase C coupled GPCR

phospholipase C cleaves PIP2 -release of IP3 and DAG IP3 releases ER Ca stores and activates Ca dependent kinase (like protein kinase C) DAG activates protein kinase C

phospholipase A2 coupled GPCR

activation of PKA2 - cleaves membrane phospholipids to produce lysophospholipid and arachidonic acid arachadonic acid converted to eicosanoids

guanylyl cyclase

receptor that increases cGMP

receptor tyrosine kinase

cascade of phosphorylation | -autophosphorylate themselves

steroid hormones

bind intracellular receptors | -cytosolic or nuclear

HRE activation

hormone response elements -once receptor activated: dimerize, bind 5' DNA sequence (HRE), initiate transcription

HREs

DNA sequence highly conserved -specificity depends on presence of receptor dissociation may occur and receptor may return to nucleus or be degraded receptor expression not induced by steroid hormone itself

amine hormones

bind cell surface receptors | -adrenoreceptors or dopamine receptors

alpha-adrenergic receptors

respond to NE

alpha -2 adrenergic receptors

GPCRs that are inhibitory - decreased cAMP

alpha-1 adrenergic receptors

coupled to phospholipase C - IP3 and DAG formation increased Ca release increased protein kinase C activity

beta-adrenergic receptors

respond to epinephrine activate GPCR to stimulation of adenylyl cyclase -increase cAMP

dopaminergic receptors

attached to DPCRs

DA-1

G protein stimulation E

DA-2

G protein inhibitory NE

thyroid hormone

similar to steroid - receptor in nucleus - binds T3, dimerizes with retinoid X receptor (RXR) - T4 deiodinated to T3 - binds HREs to initiate transcription

G-alpha-s

activate adenylyl cyclase | increase cAMP

G-alpha-i

inhibit adenylyl cyclase | decrease cAMP

G-alpha-q

activate phospholipase C increase IP3, DAG, Ca NE

guanylyl cyclase

receptor | -increases cGMP

hormone response time

ligand-gated - milliseconds GPCR - seconds kinase-linked - seconds, hours, days nuclear - hours to days

activation of insulin receptors

- binds alpha subunit of receptor (tyrosine kinase) - autophosphorylation of beta subunit - tyrosine kinases activated - cascade of phosphorylation glucose, fat, protein metabolism

timing of insulin receptor activation

seconds - glucose transporters to membrane increasing glucose uptake minutes - changes in activity of metabolic enzymes hours and days - translation and transcription achieving global changes in intracellular metabolic enzymes

sex hormones

enhance transcription when bound to receptors | -don't interact directly with DNA

mutations in steroid receptors

DNA-binding domains are similar to one another | -mutations can greatly alter hormone function

two AA substitution in glucocorticoid receptor

binding to estrogen HRE | -glucocoricoids have estrogen-like affect

steroid hormone receptors

ligand binding domain nuclear localization signal -translocation into nucleus DNA binding domain - HRE on DNA - induces transcription

protein administration

steroid administration

oral - cortisol, progesterone, estradiol transdermal - testosterone, cortisol, estradiol IV - testosterole, estradiol (emergency) IM- progesterone

amine administration

subQ or IM - Epi IV - NorEpi, Dopamine oral - thyroid