steroid biosynthesis Flashcards
is endocrine signaling long or short lasting
long lasting
lypophilic signaling molecules: steroid hormones
steroid hormones: progesterone, estradiol, testosterone, vitamin D, aldosterone, cortisol
(PET VAC)
lipophilic hormones 3 classes
steroid hormones
thyroid hormones
retinoids
lipophilic signal molecules: thyroid hormones
thyroxine
lipophilic signal molecules retinoids
retinol, retinoic acid
3 parts of intracellular receptors
DNA binding domain, ligand-binding domain, and txn-activating domain
what are steroid hormones synthesized from ___ in ___ and where
cholesterol in the smooth ER of adrenal cortex, ovaries, and testes
where do adrenal cortex, ovaries, and testis get cholesterol from
circulating LDL
de novo synthesis from acetyl coA
from cholesterol esters stored in cytoplasmic lipid droplets
acetyl coA pathway with steroids
acetyl coA X 3 = IPP
IPP can form
steroids, lipid soluble vitamins, ubiquinone, heme tails
how many IPPs do you need to make vitamin D
-how many carbons is it
6 unit, 27 carbons
what is the RL step of steroid hormone synthesis
cholesterol to pregnenolone
desmolase is enzyme used
what is a stimulator of desmolase
ACTH activates expression
LH increases activity
pregnenolone effects without conversion
- works as modulator of NT signaling in brain
- effects NMDA gluatamte receptor (memory and learning)
glucocorticoids have affinity for ___ receptors and are 100 times more concentrated
mineralcorticoid
what must pregnenolone be converted to to make other progestrogens and what enzymes are responsible
progesterone
-17a hydroxlase and 3-B hydroxysteroid dehydrogenase
progesterone is specifically converted in a tissue specif manner to
aldosterone, cortisol, estradiol and testosterone
estradiol comes from where
testosterone in ovaries, minor amt in adrenal cortex
what is formed along with testosterone in the testes and is more potent
dihydrotestosterone
conversion of testosterone to estradiol enzyme and stimulatory factor
testosterone —-aromatase—> estradiol
-occurs in ovaries, FSH is positive stimulator
where is desmolase found
only in tissues that produce steroid hormones
gonads, and adrenal cortex
21-hydroxylase deficiency
hyponatremia, hypoglycemia
-in females causes virilism (development of male secondary characterisitcs)
if have a deficiency of 17-a hydroxylase this causes what?
can be compensated by what
loss of cortisol and sex steroids
-decrease in cortisol is compensated by increased production of corticosterone (aldosterone arm)
defect in 11-B hyrdroxylase
causes hypertension due to accumulation of 11-decoxycorticosterone which has mineralcorticoid like effects
how does cortisol suppress immune system
induce production of i-kBa which helps keep NF-kB inactive in cytoplasm
- NF-kB is required for cytokines like IL-2 needed for T cell prolif
- Cortisol promotes T cell apoptosis
- decreased IL-2 and its receptor lead to inhibtion of clonal expansion of B lymphocytes as well
kidneys colon and parotid gland have receptor that has equal affinity for both mineralo and glucocorticoids, how does this tissue deal with this to prevent Na+/H20 retention
-licorice effect
Cortisol metabolized to cortisone by 11B-hydroxysteroid dehydrogenase
- cortisol has lower affinity for mineralocorticoid receptor
- licorice root contains isoflavones which inhibit this enzyme which can lead to hypertension
testosterone converted to DHT by what
-DHT has an ___ affinity for androgen receptor than testosterone
what drug inhibits the enzyme for this conversion and it treats what
testosterone —-5-a-reductase–> DHT
- DHT has higher affinity than testosterone for androgen receptor
- finasteride inhibits 5-a reductase
- used to treat beningn prostatic hyperplasia and male pattern baldness
vitamin D2,D3, calcitriol
Vitamin D2,D3 can come from diet
- Vitamin D3 produced in skin from sunlight
- Calcitriol, active form of Vitamin D, derived from D2 and D3
what stimulates calcitriol
what inhibits it
stimulated by PTH
inhibitied by calcitonin
PTH on calcitriol causes what
increased calcium and phosphate absorption from intestinal lumen
increased bone resorption
increased calcium reabsorption in kidneys
-overall increases phosphate and calcium
examples of glucocorticoids
cortisol, cortisone, corticosterone
examples of mineralocortiocis
aldosterone, 11-deoxycorticosterone
examples of estrogens
estradiol and estrone
examples of androgens
testosterone, DHEA, 5-DHT
what substrate is converted into aldosterone, what is the enzyme, and what stimulates this
corticosteron—-18-hyrdoxylase—>aldosterone
(+) angiotensin II
what is vitamin D derived from
cholesterol
vitamin D3 is converted from what by sunlight
7-dehydrocholesterol
what stimulates 1-a-hydroxylase
PTH, low phosphate, low calcium
what inhibits 1-a-hydroxylase
calcitorl (increased vitamin D has neg feedback)
glucocorticoids and infant RDS
in premature babies there is no burst of glucocorticoids to have type II alveolar cells make surfacant
-leads to infant RDS and give expecting mother glucocorticoids to treat
progesterone and pregnancy
progesterone supports pregnancy, embryogenesis and involved in maintenance of menstrual cycle
- regulates calcium channels on spermatozoa
- prepares uterus for implantation
- increases SM relaxation
- decreases maternal immune response
- prog decreases before period, labor, lactation
steroid hormones and globulins
CBG transports: plasma glucocorticoid hormones, and progesterone
SHBG transports: testosterone, DHT, and estradiol
- partially saturated with estradial in women
- fully saturated with testosterone in men
