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Endo Exam 1 > Hormone Signaling and Synthesis Pathways > Flashcards

Hormone Signaling and Synthesis Pathways Flashcards

1
Q

classes of hormones

A

protein/polypeptides
steroid
amines

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2
Q

protein hormones

A

> 100 AA - protein

<100 AA peptide

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3
Q

release of protein hormones

A 
secretory pathway
-mRNA > RER - preprohormone
-SER - cleaved to prohormone
golgi - packed in vesicle, cleaved to hormone
-exocytosis
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4
Q

constitutive synthesis

A

ECM and plasma membrane components

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5
Q

regulated synthesis

A

hormones and enzymes

-regulated at level of transcription or exocytosis

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6
Q

sources of cholesterol for steroid hormones

A

LDL

acetyl-CoA de novo

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7
Q

steroid hormones

A

lipophilic
regulated by trophic hormones from pituitary
-no intracellular stores

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8
Q

tissues that secrete steroid hormones

A

adrenal cortex

gonads

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9
Q

amine hormone synthesis?

A

from tyrosine

catecholamines and thyroid hormones

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10
Q

ovaries

A

estrogen

progesterone

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11
Q

dopamine synthesis

A

tyrosine > L-dopa > NE > E

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12
Q

thyroid hormones

A

derived from tyrosine
lipophilic** - carried on binding protein

iodination of tyrosine residues on thyroglobulin

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13
Q

thyroxine

A

T4 - de-ionated at target tissue

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14
Q

triiodothyronine

A

T3 - main effector - higher affinity for receptor

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15
Q

synthesis of thyroid hormones

A 
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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16
Q

T/S ratio

A

ration of follicular cell iodide to plasma iodide

-increases with high TSH**

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17
Q

affects of TSH

A

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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18
Q

adrenal medullary hormones

A

E and NE
-catecholamines

synthesized and stored in chromaffin granules

release stimulated by sympathetic innervation
-no negative feedback

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19
Q

chromaffin cells

A

synthesis of E and NE in adrenal medulla

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20
Q

synthesis of medullary hormones

A 
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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21
Q

circulating hormones

A

free or unbound

associated with binding protein

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22
Q

free or unbound hormones

A

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

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23
Q

hormones bound to protein

A

long-term, slow acting

fat-soluble - steroid and thyroid hormones

24
Q

thyroid hormones binding protein

A

creates hormone reservoir and extends half life

25
Q

protein hormone receptors

A

bind GPCR

-coupled to cAMP, phospholipase C, phospholipase A2

26
Q

cAMP coupled GPCR

A

activation (a-s) or inhibition (a-i) of adenylyl cyclase

affects cAMP levels

cAMP activates protein kinase A

27
Q

phospholipase C coupled GPCR

A

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

28
Q

phospholipase A2 coupled GPCR

A

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

arachadonic acid converted to eicosanoids

29
Q

guanylyl cyclase

A

receptor that increases cGMP

30
Q

receptor tyrosine kinase

A

cascade of phosphorylation

-autophosphorylate themselves

31
Q

steroid hormones

A

bind intracellular receptors

-cytosolic or nuclear

32
Q

HRE activation

A

hormone response elements

-once receptor activated:
dimerize, bind 5’ DNA sequence (HRE), initiate transcription

33
Q

HREs

A

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

34
Q

amine hormones

A

bind cell surface receptors

-adrenoreceptors or dopamine receptors

35
Q

alpha-adrenergic receptors

A

respond to NE

36
Q

alpha -2 adrenergic receptors

A

GPCRs that are inhibitory - decreased cAMP

37
Q

alpha-1 adrenergic receptors

A

coupled to phospholipase C - IP3 and DAG formation

increased Ca release
increased protein kinase C activity

38
Q

beta-adrenergic receptors

A

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

39
Q

dopaminergic receptors

A

attached to DPCRs

40
Q

DA-1

A

G protein stimulation

E

41
Q

DA-2

A

G protein inhibitory

NE

42
Q

thyroid hormone

A

similar to steroid

  • receptor in nucleus
  • binds T3, dimerizes with retinoid X receptor (RXR)
  • T4 deiodinated to T3
  • binds HREs to initiate transcription
43
Q

G-alpha-s

A

activate adenylyl cyclase

increase cAMP

44
Q

G-alpha-i

A

inhibit adenylyl cyclase

decrease cAMP

45
Q

G-alpha-q

A

activate phospholipase C
increase IP3, DAG, Ca

NE

46
Q

guanylyl cyclase

A

receptor

-increases cGMP

47
Q

hormone response time

A

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

48
Q

activation of insulin receptors

A
  • binds alpha subunit of receptor (tyrosine kinase)
  • autophosphorylation of beta subunit
  • tyrosine kinases activated
  • cascade of phosphorylation

glucose, fat, protein metabolism

49
Q

timing of insulin receptor activation

A

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

50
Q

sex hormones

A

enhance transcription when bound to receptors

-don’t interact directly with DNA

51
Q

mutations in steroid receptors

A

DNA-binding domains are similar to one another

-mutations can greatly alter hormone function

52
Q

two AA substitution in glucocorticoid receptor

A

binding to estrogen HRE

-glucocoricoids have estrogen-like affect

53
Q

steroid hormone receptors

A

ligand binding domain

nuclear localization signal
-translocation into nucleus

DNA binding domain

  • HRE on DNA
  • induces transcription
54
Q

protein administration

55
Q

steroid administration

A

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

56
Q

amine administration

A

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

Endo Exam 1 (10 decks)

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