Steroid Biosynthesis Flashcards
Synthesis of steroid hormone begins with the rate limiting step that is catalyzed by ____ to produce ____.
Enhanced by ____.
Desmolase
Pregnenolon
ACTH, LH
Pregnenolone is converted to ____ by _____ enzymes.
Progesterone
17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase
Glucocorticoids have a ____ affinity for mineralocorticoids and are ____ more concentrated
Higher
100
What enzyme converts progesterone to aldosterone and cortisol?
21-alpha-hydroxylase
17, 20-lyase aids in the formation of ____.
Estradiol and testosterone
What hormone stimulates estradiol production in ovaries by activating the enzyme aromatase?
FSH
21-hydroxylase deficiency causes what?
Symptoms?
Decrease production of aldosterone and cortisol
Hyponatremia, hypotension, hypoglycemia
Causes virilism (male secondary sex characteristics) in females because increased flow if intermediates into adrenal androgens
Classical congenital adrenal hyperplasia due to ____ deficiency.
Can be associated with Turner’s Syndrome because of decreased estradiol levels leading to increase FSH and LH.
Turner’s syndrome is due to a deleted ___ chromosome and have symptoms such as ____.
21-hydroxylase
X (45XO)
Streak ovaries
Deficiency of 17-alpha-hydroxylase cause as what?
Defect in 11-beta-hydroxylase causes what?
Loss of cortisol and sex steroids
Hypertension because accumulation of 11-decoxycorticosterone (has mineralocorticoid activity
Cortisol is metabolized to cortisone through the action of 11beta-hydxroxysteroid dehydrogenase. This is inhibited by what? Causing what?
Cortisone has a ___ affinity to mineralocorticoids.
Licorice
Hypertension due to salt retention
Lower
Active form of vitamin D?
Acts through ____ receptors targeting genes containing _____.
Calcitriol (1,25-dihydroxycholecalciferol)
Nuclear receptors
Vitamin D response element (VDRE) sequence
Describe vitamin D synthesis
Sources? Enzymes? Location?
Skin has 7-dehydrocholesterol -> exposed to sunlight -> converted to cholecalciferol (inactive vitamin D) -> converted to 25-hydroxyvitamin D by 25-hydroxylase in the liver
Ergocalciferol is another source of vitamin D in the intestine
In the kidney 1,25-dihydroxycholecalciferol (calcitriol) is synthesized by 1-alpha hydroxylase
25-hydroxycholecalciferol is hydroxylated in the ____ of the kidneys by ____ enzyme.
This generates ____.
The action of this enzyme is stimulates by ____ and low Pi; inhibited by ____
Proximal tubules
1-alpha-hydroxylase
Calcitriol
PTH; calcitriol
Women with congenital adrenal hyperplasia have what symptoms?
Fetus at risk will have excess ___ in amniotic fluid.
Treatment of adrenal hyperplasia?
Hirsutism: excess body hair
General oligomenorrhea: infrequent menstruation; greater than 35 days; infertility
Excess cortisol
Hormone replacement therapy (HRT)
Male pt with hypertension, normal genitalia or female with ambiguous genitalia present with low aldosterone, low cortisol, high testosterone, has elevation in what enzyme?
Why?
11-deoxycorticosterone
11-hydroxylase deficiency leading to inability to synthesize aldosterone and causing build up of mineralocorticoid 11-deoxycorticosterone (buildup is causing the hypertension)
____ enzyme deficiency presents in a male with ambiguous genitalia due to decreased production of testosterone
_____ enzyme deficiency presents with low levels of serum mineralocorticoids and low BP. Testosterone is elevated
17-hydroxylase
21-hydroxylase (Cyp21A2)
Accumulation of progesterone and 17-hydroxyprogesterone are due to a deficiency of what enzyme?
21-hydroxylase (Cyp21A2)
Accumulation of 11-deoxycorticosterone and 11-deoxycortisol is a result of what enzyme deficiency?
This enzyme is normally stimulated by what?
11-beta hydroxylase
Angiotensin II
Progesterone is converted into ____ which is a mineralocorticoid that binds to a MR receptor.
Excessive levels of this mineralocorticoid causes ____ syndrome.
Aldosterone
Conn syndrome -> increased blood volume and hypertension
Describe the hormonal pathway of ACTH
Cortisol levels fall -> hypothalamus produces CRH -> stimulates anterior pituitary to release ACTH -> simulates adrenal gland -> activates desmolase to begin the break down of cholesterol to cortisol
How does ACTH act on the adrenal cortex (zona fasiculata)?
How does a tumor form through this mechanism?
Binds to cell surface ACTH receptors (g-protein-coupled receptor)
Activates PKA through cAMP
Stimulates glucocorticoid steroid hormone synthesis and secretion
Tumor cells have uncoupling of G cells to receptor, yet PKA is always on, signaling cell proliferation
How does ACTH influence steroid hormone secretion?
Rapid short-term mechanisms
Stimulation of cholesterol delivery to the mitochondria where P450 (CYP) enzyme is located; this catalyzes the first step of steroidogenesis (cleave side chain of cholesterol)
Long-term effects of ACTH
Stimulates lipoprotein uptake into cells
Increases bioavailability of cholesterol in adrenal cortex
Stimulation of the transcription of the genes coding for steroidogenic enzymes
Mutations in ____ enzyme produce pseudohermaphroditism and adrenal hyperplasia
This enzyme is key in the steroidogenic pathway
17, 20 -lyase
Which form of vitamin D requires sunlight for its formation?
Cholecalciferol
