9. Steroid Hormone Biosynthesis Flashcards
Steroid hormones are derived from what?
cholesterol
What is the path from of steroid synthesis?
Cholesterol (27 carbons) -> pregnenolone (21 carbons) via desmolase.
Pregnenolone -> progesterones (THE PRECURSOR TO ALL STERIODS)
Progesterones -> corticosteroids (cortisol and aldosterone) and sex hormones (testosterone (19) and estradoil (18))
What are the other names for desmolase?
- 20, 22 Desmolase
- Cytochome P450scc
- CYP11a1
Where is desmolase found?
all steroid producing tissue (adrenal, testes, ovaries and placenta)
What catalzyes the 1st and rate-limiting step of steroid hormones
desmolase
Desmolase is positively regulated by ____________.
ACTH
& LH
What are the short-term and long-term actions of ATCH?
Short term: stimulate lipoprotein uptake in cortical cells and increases availability of cholesterol in the adrenal ctx
long term: transcribe genes that code for steroid hormones such as, cytochrome p450scc, which catalyzes the 1st step of steroidogenesis
How is ACTH in a cancer cell?
- In a normal cell, ACTH will bind to Gs GCPR: +AC -> cAMP -> PKA to produce cortisol.
- In tumor cells, the proportion of cortisol is uncoupled from ACTH.
- Constituively active PKA will continue to make cortisol even w/o ACTH binding
To go from progesterone -> aldosterone, what CYPS are needed
CYP21
CYP11B1
CYP11B2
these are types of cytochrome P450s
To go from progesterone -> cortisol, what CYPS are needed
CYP11B1
CYP17
CYP21
these are types of CYTP450
how many cyps in human genome
57
Cortisol binds and activates what?
glucocorticoid receptor (GR)
Why are glucorticoids inportant in infant respiratory distress syndrome
- During normal delivery, there is a burst of glucocorticoids that alters the bbs lung structure -> makes surfactant -> expands lungs so they can breath.
- In premature bbs, this process is defective and leads to infant. respiratory distress syndrome. This is prevented by giving mom glucocorticoids.
aldoesterone binds and activates what receptor
mineralcorticoid receptor
Patients with congenital adrenal hyperplasia present with what?
- Hirutism- excessive body hair in M and W where it does not normally grow. F patients will have general oligomenorrhea, which is infrquent menstruation and infertility.
The clinical severity of CAH depends on what?
the degree of deficiency in the enzyme that encodes steroidogenisis, causing excess or deficient production of sex steroids.
95% cases involve 21-alpha- hydroxylase. 5% involve 11B-hydroxylase.
congential adrenal hyperplasia tx
hormone replacement therapy
What are the genetics of CAH?
Autosomal recessive
If a patient has CAH with a mutant 11B-hydroxylase (CYP____), what happens?
CYP11B1
- Corticosterone precursors build up, causing an excess of androgen productions (M and F sex hormones),
- accumulation of 17-alpha- hydroxyprogesterone
- accumulation of 11-deoxycorticosterone.
Pts with CAH d/t a mutant 11B-hydroxylase will have an increase in 11-deoxycorticosterone. This will cause what?
- 11-deoxycorticosterone is a mineralcorticoid AGO. It will act like aldosterone
- Cause HTN by promoting increase Na+ and H20 retention, decrease in plasma K+,.
In patients with 11-B hydroxylase (Cyp11B1) deficiency, only. ________ and ______ would increase d/t this enzyme deficnecy. Of the two compounds, _________ has a higher affinity for MR to produce HTN.
- 11-deoxycorticosterone
- 11-deoxyxcortisol
- Of these two, 11-deoxycorticosterone has a higher affinity for MR to cause HTN.
In patients with CAD d/t 21-alpha-hydroxylase deficiency,
what hormones accumulate abnormally?
- Decreased cortisol synthesis
- Decreased aldosterone synthesis -> salt wasting
- High ACTH levels
In the blood, progesterone, 17alpha-hydroxypregenolone, 17alpha-hydroxyprogesterone.
What are the steroid hormone blood transporter proteins?
where are they made?
- CBG- corticosteroid binding globulin
- SHBG- sex steroid binding globulin
both are made in the liver.
__________ is the precursor to the following hormones: progesterne, aldosternoe, cortisol, testosterone and estradiol. Mutations in __________, prevent us from makeing these.
Pregnenolone
- CYPs
- HSDs
- Lyases
More rare forms of CAH are caused by, _____________, the enzyme that is the gateway to make sex steroid hormones.
CYP17A1 (17-alpha-hydroxylase, you will only have aldosterone production.
Isolated 17,20-lyase deficiency (ILD), the gateway to make androgens and estrogen sex steroids, causes what?
- No sex steroids; normal levels of glucocorticoids and mineralcorticoids.
- Does not result in adrenal hyperplasia or HTN.
What occurs with ILD?
- Males: underdeveloped genital, intersex, pseuhermaphroditism
- Females: reduced/no puberty, lack of secondary sex characteristics, child like appearance in adulthood.
What converts progesterone -> testosterone?
17,20 lyase
What stimulates the formation of estradoil and estrone?
- Androstenedione -> [+ FSH] stimulates aromatase in ovaries -> estrone
- Testosterone -> [+FSH] stimualtes aromatse in ovaries -> estradoil
In F, what regulates the production of GnRH?
Progesterone inhibits GHR from the hypothalamus, as well as FSH and LH release from the pituitary.
In M, what regulates the production of GnRH?
- Testosterone inhibits GnRH
- Testosterone also inhibits the release of LH from the pituitary gland,
- Inhibin inhibits the release of FSH
Vit D production happens in several different. tissue. What. are. these tissues?
1. Skin
2. liver
3. kidney
4. intestine
Cholecalciferol (vit D3) is obtained in 2 ways. What are they?
- Diet
- Skin
________ is formed exclusively. in the liver by the 25-hyroxylase enzyme (CYP____)
25-hydroxycholecalciferol is formed exclusively. in the liver by the 25-hyroxylase enzyme (CYP2R1).
Hydroxylation states of vit. D forms what?
Cholecalciferol (D3)
