Steroid Biosynthesis Flashcards
general aspects of steroid hormones
LO1
signaling molecules that alter gene transcription
- bind to intracellular receptors (transcription factor)
Types of Steroid Hormones (5)
- Progesterone
- Aldosterone
- Cortisol
- Testosterone
- Estradiol
Progesterone
- where it is synthesized
- distributed where
- function
- binds to and activates
21 carbon
gestation- supportive hormone
synthesized in adrenal gland, ovaries, and testes
distributed to uterus
fxn: mediates implantation and maintenance of pregnancy
binds to and activates progesterone receptors
Aldosterone
- where it is synthesized
- distributed where
- function
- *- binds to and activates
21 carbon
mineralcorticoid that increases Na+ and water retention and raises blood pressure
synthesized in adrenal glands
distributed to kidney tubules, colon, and parotid glands
fxn: increase Na/h20 retention, K excretion and blood pressure
binds to and activates mineralcorticoid receptors
Cortisol
- where it is synthesized
- distributed where
- function
- *-binds to and activates
21 carbon
glucocorticoid “stress” hormone that increases gluconeogenesis and blood pressure and has inflammatory effects
synthesized in adrenal glands
distributed to many organs and tissues
increase BP and Na uptake in kidney
mediates response to stress
***binds to and activates Glucocorticoid receptors
Estrogen
- where it is synthesized
- distributed where
- function
- binds to and activates
synthesized in ovaries, placenta, and adipose tissue
distributed to primary and secondary reproductive organs
mediates feminization, estrous cycle
binds and activates ERa
Androgen
- where it is synthesized
- distributed where
- function
- *-binds to and activates
synthesized in adrenal glands, ovaries, and testes
distributed to primary and secondary reproductive organs
mediates spematogenesis, male, bone maturation
binds to and activates androgen receptor
Short Term response to stress by adrenal glands
- hormone
- characteristics
Catecholamines
- increase HR
- increase BP
- liver converts glycogen to glucose and release glucose to blood
- bronchiole dilation
- increase metabolic rate
Long Term response to stress by adrenal glands
- hormone
- characteristics
Mineralcorticoids and Glucocorticoids
- retention to na and h2o by kidneys
- increase blood volume and BP
- protein and fats converted to glucose or broken down for energy
- increased blood sugar
- suppression of immune system
Where are steroid hormones derived from?
-enzyme
Cholesterol
desmolase
Steroid hormone synthesis
-pathway
LO2
cholesterol-> pregnenolone (via desmolase)-> progesterone -> corticosteroids and sex hormones
corticosteroid -> aldosterone and cortisol
sex hormones -> testosterone and estradiol
Progesterone and Pregnancy relationship
progesterone supports gestation and embryogenesis
- maintenance of menstrual cycle
Glucocorticoid and infant respiratory distress syndrome relationship
-treatment
glucocorticoid alters lung structure by stimulating surfactant production => allows air to expand in normal infants
if not glucocorticoid, leads to IRDS
- tx: give mom glucocorticoid (betamethasome, dexamethasone)
Desmolase
- nickname
- location
- function and regulation
cholesterol -> pregnenolone
found in all steroid producing tissues (adrenal, testes, ovary, placenta)
catalyzes rate limiting step
**positively regulated by ACTH
Biochemical Actions of ACTH
- short term
- long term
Short term actions
- stimulate lipoprotein uptake into cortical cells
- increase bioavailability of cholesterol in adrenal cortex
Long term
- stimulation of transcription of genes coding for steroidgenic enzymes
- P450scc- catalyzes first step of steroidogenesis (cleavage of side-chain cholesterol)
- steroid 11B hydroxylase
- associated electron transfer protein
ACTH and Cancer relationship
Normal:
ACTH-> AC-> cAMP-> PKA-> cell proliferation
Tumor cell
constitutively active PKA -> cell proliferation-> cortisol production
Congenital Adrenal Hyperplasia
- symptoms
hirsutism: excessive body hair
- oligomenorrhea- infrequent menstruation
- infertility
- HLA presentation
- excess cortisol
Congenital Adrenal Hyperplasia
- classical
- non classical
Classical
- salt wasting: dehydration, vomit, diarrhea
- ambiguous genitelia
Nonclassical
- milder than classical
- androgen excess+> precocious puberty
- asymptomatic
Adrenal Hyperplasia
- Treatment
carefully monitored hormone replacement therapy
Congenital Adrenal Hyperplasia
- mutation
90-95% involves genes for 21 hydroxylase
5% involves 11B- hydroxylase
Defect in steroid hormone syntheses
- **1. excess androgen production
- **2. 17a hydrocy progesteron accumulation
3. mutant 11b hydroxylase
4. corticosterone precursor buildup
Hypertension in CAH
11 deoxycorticosterone
- accumulates abnormally
- constitutive mineralocorticoid
- receptor (MR) agonist
- dysregulated salt and water balance
- promotes Na+ and water retention
- lowers plasma K concentration
Steroid hormone effects with 11B deficiency
only 11 deoxycoricosterone and 11 deoztcortisol levels would increase due to this enzyme
11 deoxycorticosterone has much higher affinity for MR to produce HTM
increased Na absorption in kidney => HTN
=> increased aldosterone
Congenital Adrenal deficiency
- hormone
- effects (4)
21 a hydroxylase deficiency
- reduced cortisol synthesis
- hyperplasia of adrenal cortex
- increase ACTH level
hormone accumulate abnormally in adrenal cortex, blood
- increase progesteron
- increase 17a hydroxypregnenolone
- increase 17a- hydroxyprogesterons
salt wasting
- lack of aldosterone=> high rate of sodium loss in urine
Steroid hormone blood transporter proteins (2)
- organ
- corticosteroid binding globulin
a. glycosylated globin protein
b. serine-protease- inhibitor family
c. transport/release of 80-90% of glucocorticoid hormones and progesteron - Sex steroid binding globulin
a. transport/release of testosterone, digydrotestosterone and estradiol
b. albumin binds a little bit
c. partially saturated in women
d. fully saturated by tesosterone in men
** both cbg and shbg are made in liver
Renin Angiotensin Aldosterone System (2)
-organ
SAME AS STEROIF HORMONE BLOOD TRANSPORTER PROTEIN
- corticosteroid binding globulin
a. glycosylated globin protein
b. serine-protease- inhibitor family
c. transport/release of 80-90% of glucocorticoid hormones and progesteron - Sex steroid binding globulin
a. transport/release of testosterone, digydrotestosterone and estradiol
b. albumin binds a little bit
c. partially saturated in women
d. fully saturated by tesosterone in men
**both cbg and shbg are made in liver
What is the most importatnt biochemical intermediate for steroid biosynthesis?
PREGNENOLONE
- used as substrate to produce other hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
Rare forms of CAH are caused by
*** CYP17A1 (17a hydroxylase/ 17,20 lyase)
what converts progesterone to testosterone?
17,20 lyase
isolated 17,20 lyase deficiency (ILD)
rare autosomal recessive endocrine disorder
loss of 17,20 lyase activity
impaired production of androgen and estrogen sex steroids
Regulation of steroid hormone synthesis
- stimulatory factor
- inhibitory factor
- hormones
LO3
Stimulating factors
- ACTH
- FSH
Inhibitory factor
- progesterone
- testosterone
Hormones
- GnRH
- FSH
- LH
Vitamin D synthesis
- pathway
LO4
cholecalciferol (D3) (in skin or intestine)-> 25-hydroxycholecaliferol in liver (via CYP2R1)-> 1,25 dihydroxycholecalciferil in kidey via 1a-hydroxylase
How do we obtain cholecalciferol (D3)?
- through diet
- ergocaliferol (D2) absorved in intestine - Through skin
- converted from 7- dehydrocholesterol in skin cia UV rays
IMPORTANT note in Vitamind D production
25 hydroxycalciferol is formed exclusively in LIVEr by 25- hydroxylase enzyme encoded by CYP2R1 gene
