Exam 3 Lesson 18 Flashcards
what three things do cells that synthesize steroid hormones have in common?
a. presence of multiple lipid droplets b. presence of extensive smooth ER c. presence of numerous mitochondria with “tubular” christae
what do steroidogenic tissues need from cholesterol?
Steroidogenic tissues need cholesterol as a substrate for synthesis of other steroid hormones
Where do steroidogenic tissues get their cholesterol?
From plasma lipoproteins like HDL and LDL
How do steroidogenic tissues make other steroid hormones from cholesterol?
they have enzymes that catalyze reactions that lead to synthesis of various hormones from cholesterol
what is first common biosynthetic step in cholesterol conversion to another hormone?
cholesterol to pregnenolone
Where does conversion of cholesterol to pregnenolone take place?
in the inner mitochondrial membrane
what controls the rate of steroidogenesis?
Tissue-specific peptide hormones
what is the source of cholesterol for steroid hormones (as an ingredient)?
low density lipoproteins (LDL)
How does LDL get to cells that synthesize steroid hormones?
a. Liver makes VLDL b. VLDL enters capillaries and is treated by lipoprotein lipase c. VLDL becomes IDL d. IDL goes back to liver through LDLR receptor or becomes LDL e. LDL goes back to liver to LDLR receptor or to extrahepatic cell through LDLR receptor. f. Once in extrahepatic cell, LDL is synthesized into steroid hormone
What does lipid transfer depend on in plasma membrane?
transport proteins and lipid binding proteins
Describe the lipid transfer process? How does lipid enter and exit cell?
Lipid binds to proteins to travel throughout cell, so there are lipid binding proteins for that purpose. Then there are transport proteins that create a channel on lipid membrane so that those lipid binding proteins can go in and out of cell with lipids.
Steroid hormone production: where does Acetyl Coa meet HMG Coa Reductase?
in the endoplasmic reticulum
Steroid hormone production: what does free cholesterol encounter before entering lipid droplet?
Acyl-coenzyme A: cholesterol acyltransferase (ACAT)
Steroid hormone production: what does free cholesterol become in lipid droplet?
esterified cholesterol for storage
Steroid hormone production: What happens to esterified cholesterol as it comes out of storage of lipid droplet?
it meets cholesteryl ester (CE) hydrolase, which breaks it down into free cholesterol
Steroid hormone production: what does free cholesterol meet once outside of lipid droplet?
putative cholesterol transport factors because it needs to travel in something in the cytoplasm
Steroid hormone production: Free cholesterol enters the mitochondria, where it becomes pregnenolone. What does it meet when it comes out of mito?
P450scc
Steroid hormone production: how does plasma cholesterol enter a cell?
It can enter either as HDL or LDL. The cell will have both LDLRs and HDLRs.
Steroid hormone production: What pathway does LDL take into cell?
the endocytic pathway. LDL is endocytosed, and then goes to lysosomes, where it is broken down into free cholesterol.
Steroid hormone production: what pathway does HDL take into cell?
the selective pathway. HDL enters cell and runs into cholesteryl ester (CE) hydrolase, which turns it into free cholesterol that can enter lipid droplet
Steroid hormone production: which cholesterol pathway is more common?
selective pathway
what peptide hormones regulate steroid hormone synthesis?
ACTH and gonadotropins (LH, FSH)
How do ACTH and gonadotropins stimulate steroid hormone synthesis?
they stimulate the cAMP-protein kinase A signaling cascade, which does two things: it phosphorylates cholesteryl esterase and stimulates free cholesterol transfer into inner mito
How does cholesteryl esterase help increase steroid hormone synthesis?
it converts cholesteryl esters into free cholesterol
What protein helps transfer free cholesterol into the inner mitochondria?
StAr: steroidogenic acute regulatory protein
How do kinases work with transcription factors to increase steroid hormone synthesis?
Kinases will get transcription factors to encourage the synthesis of StAr in the nucleus. StAr will be phosphorylated by kinases and bind to outer membrane of mitochondria to stimulate its production of pregnenolone.
How large is StAr? What induces its synthesis?
30 kDa protein; cAMP
what blocks Star from being synthesized?
protein synthesis inhibitors
where is StAr present?
adrenal glands, testes, ovaries
what can mutation in StAr cause?
congenital adrenal hyperplasia, a lethal disease marked by reduction in steroid hormone synthesis
Aldosterone biosynthesis: once cholesterol becomes pregnenolone in mito, what happens to it?
Pregnenolone exits mito, runs into 3beta HSD to become progesterone.
Aldosterone biosynthesis: how does progesterone turn into deoxycorticosterone?
Through 21 hydroxylase
aldosterone biosynthesis: where does pregenolone become progestorone?
ER
aldosterone biosynthesis: where does progesterone become doxycorticosterone?
ER
aldosterone biosynthesis: how does deoxycosticosterone become aldosterone?
It reenters the mito, meets aldosterone synthase, which turns deoxycorticosterone to corticosterone and corticosterone to aldosterone, which then goes out to cytosol.
aldosterone biosynthesis: what are the synthesis steps from cholesterol to aldosterone?
a. cholesterol becomes pregnenolone in mito b. pregnenolone via 3beta HDS becomes progesterone in ER c. progesterone via 21 hydroxylase becomes deoxycorticosterone in ER d. deoxycorticosterone reenters mito and via aldosterone synthase becomes first corticosterone and then aldosterone.
are steroid hormones stored in granules?
no
what happens when steroid hormones are released into circulation?
they associate with serum proteins like corticol binding p, testosterone binding p, and albumin
general structure of steroid hormone receptor?
N-terminus variable region, DNA binding domain, ligand binding domain
What role does Zinc finger motif play in transcriptional factors in steroid hormone synthesis?
DNA binding domain
To which domain does glucocorticoid hormone bind on its receptor?
the ligand binding domain (LBD)
where is the glucorticoid hormone receptor located?
it is intracellular
what happens to LBD when the hormone binds?
the ligand binding domain loses the inhibitor that is bound to it
what happens to entire glucocorticoid hormone receptor when hormone binds to it?
it translocates into the nucleus and the DBD binds to the response element on the promoter region of the DNA
In what steroidogenic tissue does synthesis of steroid hormones take place?
Adrenal cortex, testes, ovaries, placenta, liver, kidney, skin
What steroid hormones are made in liver?
Cholesterol and bile acid
Where does vitamin d synthesis take place?
Skin, liver, kidneys
what are the steps of cholesterol synthesis from acetyl
CoA
a. acetyl CoA + acetylacetyl CoA + HMG-CoA Reductase –> mevalonate –>–> isopentenyl pyrophosphate (IPP) –> farnesyl pyrophosphate –> squalene –> cholesterol
what are derivatives of isopentyl pyrophosphate during cholesterol synthesis?
isopentyl adenosine and may other isoprenoids
What are derivatives of farnesyl pyrophosphate during
cholesterol synthesis?
dolichol haem ubiquinone vitamins (A, E, and K) chlorophyll lipid-anchored proteins like Ras
what derivatives can be made from cholesterol?
vitamin D bile acids steroid hormone cholesterol esters modified proteins (hedgehog)
what are the three zones of the adrenal cortex?
medulla, zonas, and capsule
what do the zones of the adrenal cortex produce?
medulla – catecholamines
zona reticularis and fisciculata – glucocorticoids and
gonadocorticoids
zona glomerulosa - mineral corticoids
