Steroid Biosynthesis Flashcards
5 steroid hormone classes
Progestins Glucocorticoids Mineralocorticoids Estrogens Androgens
Progesterone is an example of the ______ hormone class.
Where is it synthesized, distributed, and what does it mediate?
Progestins
Synthesized in adrenal glands, ovaries, testes
Distributed to uterus
Mediates implantation and maintenance of pregnancy
Cortisol, cortisone, and corticosterone are examples of what class of hormone?
Where are they synthesized, distributed, and what do they mediate?
Glucocorticoids
Synthesized in adrenal glands
Distributed to many tissues/organs; increases BP and Na uptake in kidneys; mediates response to stress by increasing protein catabolism and gluconeogenesis and reducing inflammation
Aldosterone and 11-deoxycorticosterone are members of what hormone class?
Where are they synthesized, distributed, and what do they mediate?
Mineralocorticoids
Synthesized in adrenal glands
Distributed to kidney tubules, colon, parotid gland
Increases Na/H2O retention, K excretion, and BP
Estradiol and estrone are members of ______ hormone class
Where are they synthesized and distributed, and what do they mediate?
Estrogens
Synthesized in ovaries, placenta, adipose tissue
Distributed to primary and secondary reproductive organs
Mediate feminization, estrous cycle, inhibit testosterone synthesis
Testosterone, 5-alpha-dihydrotestosterone, and DHEA are members of what hormone class?
Where are they synthesized and distributed and what do they mediate?
Androgens
Synthesized in adrenal glands, ovaries, and testes
Distributed to primary and secondary reproductive organs and muscle
Mediate spermatogenesis, secondary male characteristics, bone maturation, and virilization
Cholesterol fate in liver
Used to synthesize bile acids
Cholesterol fate in adrenal glands, ovaries, and testes
Synthesize steroid hormones
Cholesterol fate in skin
Used to synthesize vit D
What are the main lipophilic ligands?
Steroid hormones
Fat-soluble vitamins = ADEK
Are growth factors hydrophilic or lipophilic ligands?
Hydrophilic
Precursor/starting material to cholesterol synthesis
Sterane ring
What are some examples of cholesterol-based lipophilic signaling molecules/ligands?
Cortisol Estradiol Thyroxine Testosterone Vitamin D3 Retinoic acid (makes Vit A)
T/F: most signaling molecules are hydrophobic and readily diffuse across the membrane
False, most are hydrophilic and require cell surface receptors
Would you classify steroid signaling as fast or slow responses?
Slow - because most of them initiate or repress gene expression which takes time
Steroid hormones are synthesized from cholesterol in the smooth ER of the adrenal cortex, ovaries, and testes
Where do these tissues obtain cholesterol?
Circulating LDL
De novo synthesis from acetyl CoA
Cholesterol esters stored in cytoplasmic lipid droplets
Which of the following requires the most 5-carbon IPP units to synthesize?
A. Vitamin A B. Vitamin D C. Vitamin E D. Vitamin K E. Vitamin B
B. Vitamin D
Requires 6 IPP units, while vit A, E, and K require 4. Vitamin B is water soluble
The synthesis of steroid hormones begins with the RATE-LIMITING step catalyzed by ________, an enzyme that incorporates a carbonyl group on the D ring of cholesterol and cleaves off a 6-carbon piece of its side chain to form ____________
Desmolase
Pregnenolone
The rate limiting step of steroid hormone synthesis (the conversion of cholesterol to pregnenolone via RL enzyme desmolase) MUST be regulated. What is an important positive regulator of desmolase?
ACTH
Pregnenolone is an alcohol that acts as a modulator of NT signaling in the brain without being converted to other steroids. It affects the NMDA glutamate receptor involved in memory and learning.
Pregnenolone must be converted to _______ for synthesis of other proestrogens, this is done with enzymes _______ and __________
Progesterone
17-alpha-hydroxylase
3-beta-hydroxysteroid dehydrogenase
Once pregnenolone is converted to progesterone via 17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase, what are the possible end products of steroid hormone synthesis?
17-alpha hydroxylase is involved in multiple arms of the steroid hormone synthesis pathway, so possible outcomes include:
Mineralocorticoids
Glucocorticoids
Estrogens
Androgens
What is unique about glucocorticoids as they relate to mineralocorticoids, and how do they compare to mineralocorticoids in terms of concentration?
Glucocorticoids have affinity for mineralocorticoid receptors and are 100 times more concentrated than mineralocorticoids
Which of the following is progesterone specifically converted to in a tissue specific manner?
A. Aldosterone in the adrenal cortex
B. Cortisol in the adrenal cortex
C. Estradiol from testosterone precursor in the ovaries
D. Testosterone and dihydrotestosterone in testes
E. All of the above
E. All of the above
Which of the following is most essential to formation of aldosterone or cortisol (i.e., not the enzyme important in other common pathways)
A. 21-alpha-hydroxylase B. 17,20-lyase C. 17-beta-hydroxysteroid dehydrogenase D. Aromatase E. 5-alpha reductase
A. 21-alpha-hydroxylase
Which of the following is most essential to the formation of androgens and estrogens (i.e., not the enzyme common to other hormone pathways)?
A. 21-alpha-hydroxylase B. 17,20-lyase C. 17-beta-hydroxysteroid dehydrogenase D. Aromatase E. 5-alpha reductase
B. 17,20 lyase
T/F: Desmolase is only found in tissues that produce steroid hormones, such as gonads and adrenal cortex
True
What specific type of hormone stimulates expression and activity of desmolase?
Peptide hormones
What are 3 examples of peptide hormones that stimulate the action of desmolase, where are they located, and what activates them?
ACTH - secreted from pituitary gland in stressful conditions; activated by corticotropin-releasing hormone (CRH) from hypothalamus
LH - secreted from pituitary gland; activated by gonadotropin-releasing hormone (GnRH) from hypothalamus
FSH - secreted from pituitary gland; activated by GnRH from hypothalamus
FSH in females affects menstruation, and stimulates estradiol production by activating the enzyme _____
Aromatase
A relatively common inherited defect is a deficiency in 21-hydroxylase enzyme. What does this lead to?
Hyponatremia and hypotension d/t decreased production of aldosterone
Hypoglycemia d/t decreased production of cortisol
Causes virilism in females
21-hydroxylase deficiency may lead to virilism in females. What is virilism?
Development of male secondary characteristics
21-hydroxylase deficiency may lead to virilism in females. How/why does this happen?
Occurs d/t an increased flow of intermediates into adrenal androgens
Turners syndrome is the most common cause of monosomy and typically result from ______ during meiosis 1
It may be uniformly present, or present as ______ due to nondisjunction that occurs during a portion of embrylogic development
In addition, it may result from a partially rather than fully deleted ____ chromosome
Nondisjunction
Mosaicism
X
Patient presentation and pathogenesis of turner’s syndrome
Presentation: short stature, webbed neck, shield chest, wrist and ankle edema
Pathogenesis: decreased estradiol leads to increased FSH and LH buildup and normal GH and insulin like growth factor
A standard 30-cell karyotype analysis is required for dx of Turner’s syndrome, in order to exclude ______
Diagnosis is confirmed by presence of a _____ cell line, or a cell line with deletion of the short arm of the ____ chromosome
A _____ phenotype excludes the dx, regardless of karyotype
Mosaicism
45,X; X
Male
A deficiency in 17-alpha-hydroxylase is rare. What effect would this have?
Causes loss of cortisol and sex steroid hormones
[However, decrease in cortisol is compensated by increased production of corticosterone]
What are the effects of 11-beta-hydroxylase deficiency?
Hypertension, due to accumulation of 11-deoxycorticosterone, which has mineralocorticoid activity
Defects in 11-beta-hydroxylase lead to an increase in ONLY 2 hormones, what are they?
11-deoxycorticosterone
Testosterone
______ is a glucocorticoid that is also known as hydrocortisone
Cortisol
Cortisol is involved in suppression of the immune system in several ways. In particular, it promotes T cell apoptosis via decreased cytokine _____ and its receptor, leading to an inhibition of ______ ______ of B cells as well
IL-2
Clonal expansion
Mineralocorticoid target tissues such as kidneys, colon, and parotid gland contain a receptor with equal affinity for both mineralo-and glucocorticoids. These tissues must avoid Na/H2O retention and thus must metabolize cortisol to cortisone through the action of ____________ enzyme
Cortisone has much lower affinity for the mineralocorticoid receptor. Natural ______ contains isoflavones which are inhibitors of the above enzyme, so consumption of this product can lead to HTN d/t salt retention
11-beta-hydroxysteroid dehydrogenase
Licorice
The androgenic potency of testosterone is amplified by its conversion to DHT, mediated by the enzyme ________
DHT has a much ______ affinity than testosterone for the androgen receptor, so an inhibitor of the above enzyme (finasteride) is used to treat BPH
5-alpha reductase
Higher
What is the active form of vitamin D
Calcitriol (1,25 dihydroxycholecalciferol)
Calcitriol, the active form of vitamin D, is derived from vitamins D2 (__________), and D3 (__________)
Where are these derived from?
D2 = ergocalciferol - from dietary sources, converted to D3 in intestine
D3 = cholecalciferol - produced in skin via UV irradiation
Once cholecalciferol (D3) is produced in skin and intestinal cells, it is brought to the liver and converted to ___________ via __________ enzyme
25-hydroxycholecalciferol; 25-hydroxylase
Supplemental vitamin D3 must reach the _____ to be effective
Liver
Once 25-hydroxycholecalciferol is produced in the liver, it is hydroxylated in the ______ by ______ enzyme to become ______
Proximal tubules of the kidneys
1-alpha-hydroxylase
1,25-dihydroxycholecalciferol (Calcitriol)
What factors stimulate and inhibit the action of 1-alpha-hydroxylase in the formation of calcitriol?
Stimulated by PTH and low blood [PO4]
Inhibited by calcitriol
Actions of calcitriol (active vitamin D)
Stimulates intestinal cells to increase absorption of Ca and PO4 from lumen
Increase reabsorption of Ca by kidneys
Promote resorption of Ca from bone
Resulting effect is elevation in blood Ca and phosphate levels
Both classic and non-classic forms of adrenal hyperplasia are caused by deficiencies in the adrenal enzymes used to synthesize _________. This results in increased production from the adrenal gland of both _______ precursors and _________
Glucocorticoids; cortisol; androgens
Women with mild congenital adrenal hyperplasia often present with _______, which is characterized by excess body hair where it is normally absent, such as chin or chest, face or body
female patients also present with infertility and/or general _______, which is infrequent menstruation
Hirsutism
Oligomenorrhea
Diagnosing a fetus at risk for congenital adrenal hyperplasia requires using HLA-Ag haplotypes to demonstrate excess _____ precursors in amiotic fluid
Cortisol
Patient treatment for adrenal hyperplasia
Carefully monitored HRT
_______ is a condition characterized by excess levels of aldosterone, increased blood volume, and hypertension
Conn syndrome
Hydrocortisone, cortisone, 11-deoxycorticosterone, testosterone, and aldosterone all have some level of ____________ ligand activity
Increased levels of any of these compounds would cause increased Na absorption in the kidneys and hence produce ______
Mineralocorticoid (MR)
Hypertension
11-beta hydroxylase deficiency results in DECREASED aldosterone synthesis, so why does this condition result in hypertension?
Because only 11-deoxycorticosterone and 11-deoxycortisol levels increase, and of these 2 compounds 11-deoxycorticosterone has much higher affinity for MR to produce HTN
Does ACTH influence steroid hormone secretion quickly, or does it take a long time?
Quickly; ACTH is hydrophilic, binds GPCR and exerts effects using rapid, short-term mechanism (within minutes)
Cyp17A1, of the cytochrome p450 family, is the SAME as the _____ enzyme responsible for producing progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens
17,20 lyase
What form of vitamin D is found exclusively in the liver?
25-hydroxycholecalciferol
