Steroids

Question 1

Starting material

Answer 1

Cholesterol of endogenous synth (need LPL delivery)

Question 2

Steroid nucleus

Answer 2

Indestructible; modifications can be addition of hydroxy group, reduction/oxidation of side groups, cyclicize ring A (estrogens)

Question 3

Steroid pathway

Answer 3

Primary synth site is adrenal cortex with CNS control.

On paper

Question 4

Structural features and Biosynth

Answer 4

Chol nucleus is indestructible, side chain shortened between C20 and C22 (2Cs = Progesterone and corticosterone; lost = Androgens and estrogens).

OH on C3 ring A on all steroids. All stem from pregnalone, only 1 dehydration produces progesterone (all other O2 functions involve Cyt p450). Mineralcorticoids have aldehyde at C18

Question 5

Androgens

Answer 5

From testis, some adrenal and theca cells

Question 6

Testosterone

Answer 6

Major androgen from leydig cells; precursor to more active DHT and estradiol, Androstenodione = major androgen from adrenal cortex

Question 7

Estrogen

Answer 7

Directly from Testosterone, Pre meno from granulosa cells of ovaries and preg = placenta
Menopause = estrogens as estrone from adrenal
Males = microsomal aromatase in liver, skin, and brain

Question 8

Glucocorticoids

Answer 8

Regulate energy metabolism

Question 9

ZF

Answer 9

Produces Cortisol and Corticosterone

Question 10

Ant Pit Synth

Answer 10

CRH induced ACTH synth = stress hormone, increases cAMP inducing cortisol synth

Question 11

Cortisol

Answer 11

Metab and inflamm control

Question 12

Mineralcorticoids

Answer 12

Salt metabolism (aldosterone). From ZG (outer lyr), secretion induced by low Na/K ratio and angiotensin 2

Question 13

LH

Answer 13

Induces testosterone, est, progesterone, ovulation

Question 14

FSH

Answer 14

secretion of estorgens or androgens, sperm genesis

Question 15

ACTH

Answer 15

glucocorticoid secretion

Question 16

Critical Steps in Synth 1

Answer 16

Chol to pregnenolone: Side chain cleaved via Desmolase

Via NADPH and CytP450

Question 17

Critical Steps in Synth 2

Answer 17

Pregnenolone oxidized to progesterone: sole non-p450 step, precursor to all
Via 3-B-dehydrogenase, rqrs NAD+

Def = no sex steroids, FM genitals, increased urine salt, early death

Question 18

Critical Steps in Synth 3

Answer 18

Pregnenolone: 2 paths to sex steroids

1. Preg ox to Progesterone - loses stub to androstenedione
2. Preg loses stub then oxidized to DHEA and Androstenedione

Question 19

Critical Steps in Synth 4

Answer 19

Androgens to Estrogen

Androstenedione/testosterone to estrone/estradiol via aromatase cyclized ring A

Question 20

Critical Steps in Synth 5

Answer 20

Progesterone to cortisol via p450

17alphahydroxy to 21alphahydroxy to 11betahydroxylase = glucocorticoids which increase gluconeogenesis

Question 21

Critical Steps in Synth 6

Answer 21

Progesterone to Aldosterone
CYP21 to CYP11B1 to CYP11B2
Def CYP21 = most common CAH

Question 22

Defects in steroid production

Answer 22

Causes metabolic and developmental abnormalities, most important = affect on androgens as they mediate virilization. Most common: (1) Increased ACTH leads to tissue compensation for def downstream enzyme and loss of product and neg feedback balance. (2) Def enzyme shareable by 2 sequences (CYP21 and CYP11B)

Question 23

3-B-hydroxysteroid dehyd def

Answer 23

No steroids, salt excretion in urine and hypotension. Patients with GM genitalia. Blocks Preg to Prog step

Question 24

17-alpha-hydroxylase def

Answer 24

No sex or cortisol, increased mineralcorticoids - Na and H2O retention - hypertension. Patients with FM genitalia and unable to mature

Question 25

21-alpha-hydroxylase def

Answer 25

Most common, no mineral or glucocorticoids (classic) or def (nonclassic). increased ACTH leads to increased androgen synth leading to masculization of external genitalia in FMs and early virilization in males

Question 26

11-Beta-hydroxylase def

Answer 26

Decreased serum cortisol, aldosterone, and corticosterone. Increased production of deocycorticosterone leads to fluid retention and decreased RAAS but with hypertension. Masculization and virilization present

Question 27

5-alpha reductase def

Answer 27

Abnorm sexual development, norm = DHT for testosterone (required for development of male external genitalia at dev). Leads to FM at birth and at puberty virulence occurs and normal proceeds

Question 28

CAH cadence

Answer 28

1 in ten = HTN = Increased mineral and dec andro

1 in one = viril = inc andro and dec mineral

Question 29

Cushings syndrome

Answer 29

Hypercorticism leads to increased ACTH die to adenoma of pit gland leads to corticosteroid overproduction = obesity and moon face

Question 30

Addisons Disease

Answer 30

Hypocorticism in adults. TB or Autoimmune leads to bilateral destruction of adrenal cortex. Resembles 3BD def with salt wasting = death due to circ collapse and Na loss. Assoc with DM1 or metastasis of lung cancer leading to reduced glucocorticoids and mineral = hypoglycemia, Na imbalance, hypotension

Question 31

Action of steroid hormones

Answer 31

All R are IC, lipid soluble so crosses membrane and binds R in cytosol to nucleus to upreg transC

Question 32

Elimination of steroids

Answer 32

Physio elimination through OH groups to glucoronate or SO3 which increases solubility and excreted through urine