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*GIGU I > 34. Steroid Biosynthesis > Flashcards

34. Steroid Biosynthesis Flashcards

1
Q

5 steroid hormone classes

A 
Progestins
Glucocorticoids
Mineralocorticoids
Estrogens
Androgens
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2
Q

Progesterone is an example of the ______ hormone class.

Where is it synthesized, distributed, and what does it mediate?

A

Progestins

Synthesized in adrenal glands, ovaries, testes

Distributed to uterus

Mediates implantation and maintenance of pregnancy

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3
Q

Cortisol, cortisone, and corticosterone are examples of what class of hormone?

Where are they synthesized, distributed, and what do they mediate?

A

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

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4
Q

Aldosterone and 11-deoxycorticosterone are members of what hormone class?

Where are they synthesized, distributed, and what do they mediate?

A

Mineralocorticoids

Synthesized in adrenal glands

Distributed to kidney tubules, colon, parotid gland

Increases Na/H2O retention, K excretion, and BP

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5
Q

Estradiol and estrone are members of ______ hormone class

Where are they synthesized and distributed, and what do they mediate?

A

Estrogens

Synthesized in ovaries, placenta, adipose tissue

Distributed to primary and secondary reproductive organs

Mediate feminization, estrous cycle, inhibit testosterone synthesis

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6
Q

Testosterone, 5-alpha-dihydrotestosterone, and DHEA are members of what hormone class?

Where are they synthesized and distributed and what do they mediate?

A

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

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7
Q

Cholesterol fate in liver

A

Used to synthesize bile acids

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8
Q

Cholesterol fate in adrenal glands, ovaries, and testes

A

Synthesize steroid hormones

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9
Q

Cholesterol fate in skin

A

Used to synthesize vit D

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10
Q

What are the main lipophilic ligands?

A

Steroid hormones

Fat-soluble vitamins = ADEK

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11
Q

Are growth factors hydrophilic or lipophilic ligands?

A

Hydrophilic

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12
Q

Precursor/starting material to cholesterol synthesis

A

Sterane ring

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13
Q

What are some examples of cholesterol-based lipophilic signaling molecules/ligands?

A 
Cortisol
Estradiol
Thyroxine
Testosterone
Vitamin D3
Retinoic acid (makes Vit A)
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14
Q

T/F: most signaling molecules are hydrophobic and readily diffuse across the membrane

A

False, most are hydrophilic and require cell surface receptors

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15
Q

Would you classify steroid signaling as fast or slow responses?

A

Slow - because most of them initiate or repress gene expression which takes time

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16
Q

Steroid hormones are synthesized from cholesterol in the smooth ER of the adrenal cortex, ovaries, and testes

Where do these tissues obtain cholesterol?

A

Circulating LDL

De novo synthesis from acetyl CoA

Cholesterol esters stored in cytoplasmic lipid droplets

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17
Q

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
A

B. Vitamin D

Requires 6 IPP units, while vit A, E, and K require 4. Vitamin B is water soluble

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18
Q

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 ____________

A

Desmolase

Pregnenolone

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19
Q

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?

A

ACTH

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20
Q

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 __________

A

Progesterone

17-alpha-hydroxylase

3-beta-hydroxysteroid dehydrogenase

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21
Q

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?

A

17-alpha hydroxylase is involved in multiple arms of the steroid hormone synthesis pathway, so possible outcomes include:

Mineralocorticoids
Glucocorticoids
Estrogens
Androgens

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22
Q

What is unique about glucocorticoids as they relate to mineralocorticoids, and how do they compare to mineralocorticoids in terms of concentration?

A

Glucocorticoids have affinity for mineralocorticoid receptors and are 100 times more concentrated than mineralocorticoids

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23
Q

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

A

E. All of the above

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24
Q

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

A. 21-alpha-hydroxylase

25
Q

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
A

B. 17,20 lyase

26
Q

T/F: Desmolase is only found in tissues that produce steroid hormones, such as gonads and adrenal cortex

A

True

27
Q

What specific type of hormone stimulates expression and activity of desmolase?

A

Peptide hormones

28
Q

What are 3 examples of peptide hormones that stimulate the action of desmolase, where are they located, and what activates them?

A

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

29
Q

FSH in females affects menstruation, and stimulates estradiol production by activating the enzyme _____

A

Aromatase

30
Q

A relatively common inherited defect is a deficiency in 21-hydroxylase enzyme. What does this lead to?

A

Hyponatremia and hypotension d/t decreased production of aldosterone

Hypoglycemia d/t decreased production of cortisol

Causes virilism in females

31
Q

21-hydroxylase deficiency may lead to virilism in females. What is virilism?

A

Development of male secondary characteristics

32
Q

21-hydroxylase deficiency may lead to virilism in females. How/why does this happen?

A

Occurs d/t an increased flow of intermediates into adrenal androgens

33
Q

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

A

Nondisjunction

Mosaicism

X

34
Q

Patient presentation and pathogenesis of turner’s syndrome

A

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

35
Q

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

A

Mosaicism

45,X; X

Male

36
Q

A deficiency in 17-alpha-hydroxylase is rare. What effect would this have?

A

Causes loss of cortisol and sex steroid hormones

[However, decrease in cortisol is compensated by increased production of corticosterone]

37
Q

What are the effects of 11-beta-hydroxylase deficiency?

A

Hypertension, due to accumulation of 11-deoxycorticosterone, which has mineralocorticoid activity

38
Q

Defects in 11-beta-hydroxylase lead to an increase in ONLY 2 hormones, what are they?

A

11-deoxycorticosterone

Testosterone

39
Q

______ is a glucocorticoid that is also known as hydrocortisone

A

Cortisol

40
Q

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

A

IL-2

Clonal expansion

41
Q

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

A

11-beta-hydroxysteroid dehydrogenase

Licorice

42
Q

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

A

5-alpha reductase

Higher

43
Q

What is the active form of vitamin D

A

Calcitriol (1,25 dihydroxycholecalciferol)

44
Q

Calcitriol, the active form of vitamin D, is derived from vitamins D2 (__________), and D3 (__________)

Where are these derived from?

A

D2 = ergocalciferol - from dietary sources, converted to D3 in intestine

D3 = cholecalciferol - produced in skin via UV irradiation

45
Q

Once cholecalciferol (D3) is produced in skin and intestinal cells, it is brought to the liver and converted to ___________ via __________ enzyme

A

25-hydroxycholecalciferol; 25-hydroxylase

46
Q

Supplemental vitamin D3 must reach the _____ to be effective

A

Liver

47
Q

Once 25-hydroxycholecalciferol is produced in the liver, it is hydroxylated in the ______ by ______ enzyme to become ______

A

Proximal tubules of the kidneys

1-alpha-hydroxylase

1,25-dihydroxycholecalciferol (Calcitriol)

48
Q

What factors stimulate and inhibit the action of 1-alpha-hydroxylase in the formation of calcitriol?

A

Stimulated by PTH and low blood [PO4]

Inhibited by calcitriol

49
Q

Actions of calcitriol (active vitamin D)

A

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

50
Q

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 _________

A

Glucocorticoids; cortisol; androgens

51
Q

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

A

Hirsutism

Oligomenorrhea

52
Q

Diagnosing a fetus at risk for congenital adrenal hyperplasia requires using HLA-Ag haplotypes to demonstrate excess _____ precursors in amiotic fluid

A

Cortisol

53
Q

Patient treatment for adrenal hyperplasia

A

Carefully monitored HRT

54
Q

_______ is a condition characterized by excess levels of aldosterone, increased blood volume, and hypertension

A

Conn syndrome

55
Q

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 ______

A

Mineralocorticoid (MR)

Hypertension

56
Q

11-beta hydroxylase deficiency results in DECREASED aldosterone synthesis, so why does this condition result in hypertension?

A

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

57
Q

Does ACTH influence steroid hormone secretion quickly, or does it take a long time?

A

Quickly; ACTH is hydrophilic, binds GPCR and exerts effects using rapid, short-term mechanism (within minutes)

58
Q

Cyp17A1, of the cytochrome p450 family, is the SAME as the _____ enzyme responsible for producing progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens

A

17,20 lyase

59
Q

What form of vitamin D is found exclusively in the liver?

A

25-hydroxycholecalciferol

*GIGU I (67 decks)

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