Intro/Steroidogeneis Flashcards
what are all hypothalamic and pituitary hormones made up of?
Proteins and peptides
What is the bond in insulin and what is the fragment after prohormone is cleaved?
Sulfide bonds
- C-Peptide
Where are steroid hormones produced?
Gonads
Adrenals
Placenta
Are steroid hormones produced on demand or stored in vesicles?
Produced on demand
- which is why they go to increase at the DNA level
What are the amine hormones?
Catecholamines
Thyroid
What AA are the amine hormones made from?
Tyrosine
What are the steroid hormones?
Androgens Progesterones Mineralcocorticoids Glucocorticoids Estrogens - form homodimers with receptors
What are the molecules that use Retinoid X receptors? Where do they act?
Thyroid Vit D Eicosinoids (Prostaglandins) - act on a DNA response element - Form Heterodimers instead of homodimers
What is phase 1 of metabolism of hormones? Where does it happen?
Oxidation
- by liver
What is phase 2 of metabolism of hormones?
Sulfation
Methylation
Glucuronidation–> facilitates biliary secretion
What size molecular weight cause metabolites to be secreted in bile?
> 300 g/mol
Both polar and lipophilic
What is the rate limiting step in the production of steroids?
Cholesterol to pregnenolone
- Which is done by P450scc
- Which resides inside the mitochondrial matrix
What is the protein that carries cholesterol from OMM to IMM to allow for the function of P450scc to make pregnenolone?
STAR protein
- Steriodogenic acute regulatory protein
Where does STAR get cholesterol from?
- LDL-derived cholesterol
- cholesterol taken up by the scavenger receptor SRB1 3. cholesterol that is synthesized de novo in the ER
- as well as cholesterol that is derived from lipid droplets on hydrolysis of cholesteryl esters by hormone sensitive lipase (HSL).
What is Wolman Disease?
Inherited mutation in Lysosomal Acid lipase
What is the histological finding in Wolman disease?
Lipid engorged macs
- which can infiltrate organs and cause organ death/failure
What is congenital lipoid adrenal hyperplasia?
Mutation in StAR
What are the phenotypes of Lipoid CAH?
Female external genitalia
Salt wasting
Destruction of endocrine tissue due to fat accum
What converts Pregnenolone to progesterone?
3-Beta Hydroxy steroid dehydrogenase
What converts prenenonlone to 17 alpha hydroxy pregnenolone? Then to DHEA?
CYP17
- Then CYP17 again to DHEA
What does DHEA stand for? Another name for it?
Dehydroepiandrosterone
-Androgens
What can be made from progesterone?
Androgens
Cortisol
Aldosterone
What is the process is making aldosterone from progesterone?
- Progesterone–> 11 deoxycorticosterone by CYP21
- 11 deoxycorticosterone–> Corticosterone by CYP11B1
- Corticosterone–> Aldosterone by aldosterone synthase
What is another name for CYP17?
17 alpha hydroxylase
What is another name for CYP21?
21 Alpha hydroxylase
What is another name for CYP11B1?
11 beta hydroxylase
How does one make cortisol from progesterone?
- Progesterone–> 17 alpha hydroxy-progesterone by CYP17
- 17 alpha hydroxy-progesterone–> 11 Deoxycortisol by CYP21
- 11 Deoxycortisol –> to Cortisol by CYP11B1
What causes an increase in CRH?
Environmental stimulus
- that leads to increase in Ach and Serotonin
- leads to increase CRH
what is the second messenger of the binding of ACTH to the adrenal glands?
increase in cAMP
- PKA increase
- Many affects
What are the affects of increase PKA in a adrenal gland cell?
Increase SCARB2
Increase LDLr endocytosis
Increase free cholesterol
and increase CYP11A1
Where does the actions of Pregnenolone to 11-deoxycortisol and same to cortisol happen?
Cytoplasm
Nucleus respectively
What regulates cortisol synthesis enzymes?
cAMP
What happens to the binding of cortisol at the GRE?
Increase Transcriptional co-activators
RNA polymerase II
PEPCK
