Steroid Biosynthesis Flashcards
What can you inject infants to prevent RDS?
glucocorticoids
What drops before labor and menstruation and opens Ca++ channels in spermatozoa?
progesterone
All steroid hormones are synthesized from _____ in the _____
cholesterol
adrenal cortex
What RLS converts cholesterol to pregnenolone?
desmolase
–>cytochrome P450 family
What stimulates desmolase activity?
ACTH
–>cholesterol to pregnenolone (adds C=O)
Where is desmolase found?
all steroid-producing tissues
–>adrenal, testes, ovary, placenta
What is the most important biochemical intermediate that is used as a substrate for steroid hormone synthesis?
pregnenolone
What can be made from pregnenolone?
progesterone aldosterone cortisol testosterone estradiol
What binding protein transports most steroid hormones in circulation?
sex hormone binding globulin (SHBG) and albumin
What mineralocorticoid does Angiotensin II stimulate?
Aldosterone
What group of conditions are characterized by deficiencies in adrenal enzymes used to synthesize glucocorticoids?
adrenal hyperplasias
What are consequences of adrenal hyperplasia?
- life-threatening sinus and pulmonary inf
- orthostatic syncope
- shortened stature
- severe acne
What are sx women experience with mild congenital adrenal hyperplasia?
hirsutism
general oligomenorrhea
infertility
How to determine if fetus is at risk for congenital adrenal hyperplasia?
- human leukocyte antigen haplotype
- excess cortisol precursors in amniotic fluid
What can be used as treatment for adrenal hyperplasia
Hormone replacement therapy
What enzyme deficiencies can cause adrenal hyperplasia?
21-hydroxylase
–> no aldosterone
11-B hydroxylase
–> no cortisol
What does a 21-hydroxylase deficiency cause buildup of?
progesterone
–>aldosterone pathway
17 hydroxyprogesterone
–>cortisol pathway
What does a 11B- hydroxylase deficiency cause buildup of?
Deoxycorticosterone
–>aldosterone pathway
11-Deoxycortisol
–>cortisol pathway
Describe primary aldosteronism?
adrenal cortex produces too much aldosterone
- -> retention of sodium and water to extreme levels
- ->excretion of H and K
HTN
Describe Conn Syndrome
–>type of primary aldosteronism
excess secretion of aldosterone
retention of sodium
loss of potassium
HTN
All steroids that activate mineralocorticoid receptors cause what?
retention of sodium
–>HTN
How does 11-B hydroxylase deficiency cause HTN?
decreased aldosterone synthesis, however deoxycorticosterone has high affinity for mineralocorticoid receptor–> retention of Na and HTN
What glucocorticoid causes immunosuppression?
cortisol
–> gets rid of NF-kB
What does ACTH stimulate the production of?
cortisol
–>when level falls, CRH->ACTH->cortisol in fasciculata
How does ACTH activate secretion of cortisol?
it is a G protein, so:
adenylyl cyclase–> cAMP–>protein kinase A
How does a tumor cell bypass activation by ACTH to produce cortisol?
PKA (protein kinase A)
constituitively active
In addition to activating cortisol production, what else does ACTH influence?
steroid hormone secretion
–> + cholesterol delivery to mito where desmolase is
transcription of genes encoding for steroidogenic enzymes
What enzyme is crucial to the steroid hormone pathway?
17,20-lyase
–>AKA CYP17A1
What are the precursors of androgen production?
17-a-hydroxyprogesterone
hydroxypregenolone
Where is 25-hydroxycholecalciferol exclusively found?
liver
Where is calcitrol synthesized?
active form of vitamin D
kidney via 1a-hydroxylase
What does 7-dehydrocholesterol make?
found in skin
vitamin D3 (cholecalciferol)
How do you get low aldosterone and high androgens?
11-B hydroxylase deficiency
–>since can’t make aldosterone or cortisol, intermediates shift to androgen pathway
