Hormone Action IV

Question 1

what are the “steriodogenic” tissues in the body?

what steroids do they produce?

Answer 1

• adrenal cortex
  
  • zona glomerulosa - aldosterone
  • zona fasculata & reticularis - glucocorticoid (cortisol)
  • zona reticularis - andogens (DHEA, andorstenedione)
• testis
  
  • testosterone
• ovary
  
  • estrogens (estradiol, estriol, estrone)
  • progesterone

Question 2

what do all steroids have in common?

Answer 2

• derived from cholesterol
• contain cyclopentanophenanthrene ring

Question 3

how many carbons are in cholesterol?

what about cortisol, testosterone and estrogen

Answer 3

• cholesterol - 27 C
  
  • cortisol - 21 C
  • testosterone - 19 C
  • estrogen - 18 C

Question 4

in what organelle does steroid synthesis occur?

why is this important?

Answer 4

in the mitochondria

• this is impt because it requires that STAR (steroidogenic acute regulatory protein) transports cholesterol from the plasma the mitochondira

Question 5

the rate limiting step of steroid hormone synthesis?

• is done by what enzyme?
• requires what cofactors?
• occurs where?

Answer 5

• cholesterol side chain cleaveage (irreversible)
  
  • cleavage of cholesterol (27 C) to a 21 C molecule + 6 C molecule
    
    • 21 C molecule = pregnelone
    • 6 C molecule = isocaproaldehyde
  • by: cholesterol-20,22 desmolase
    
    • • ACTH-dependent esterase
  • in mitochondria (of steriogenic tissues)

Question 6

after pregnenolone + isocaproaldehyde are formed, where are they further processed to yield steroid hormones?

Answer 6

in the smooth ER

Question 7

mineralcorticoid synthesis

• occurs where?
• depends on what critical enzymes?
• has what roles in the body?

Answer 7

aka aldosterone

• in the zona glomerulosa (of the adrenal cortex)
• depends on:
  
  • 3B-hydroxysteroid dehydrogenase
  • 12-hydroxylase
  • 11B-hydroxylase
  • 18-hydroxylase & 18-hydroxydehydrogenase (aldosterone synthase) = aldsterone synthase
    
    • ​ONLY present in zona glomerulosa.
• inc Na / dec K+

Question 8

glucocorticoid synthesis

• occurs where?
• depends on what enzymes?
• has what role in the body?

Answer 8

= cortisol

• mostlhy in zona fasculata (spongiocytes) of adrenal cortex;
• depends on 17a-hydroxylase, part of P450c17 protein
• serve to
  
  • regulate carbohydrate / FA metabolism
  • immunosuppress

Question 9

androgen synthesis

• occurs where?
• relies on what key enzymes?
• produeces what steroids?
• that have what biologic effects?

Answer 9

• in zone reticularis of adrenal cortex
• depends on 17, 20 lyase (17,120 desmolase), part of P450c17 protein
• produces:
  
  • DHEA > androstenedione
    
    • yield to testosterone –> estrogen = sex effects

Question 10

testosterone synthesis

• occurs where?
• under what regulation?
• depends on what enzymes?
• has what rate limiting step?
• has what effects?

Answer 10

• in leydig cells (in the testicular interstitium)
• under regulation of LH (from GnRH)
• synthesis:
  
  • unique enzyme: 17B-hydroxysteroid hydrogenase: androgens –> testosterone
    
    • ​thus, depends on 17,20-lyase
  • rate limiting step: STAR (moves cholesterol into mitochondria)
• roles: secondary sex characteritics

Question 11

dihydrotestosterone (DHT)?

• is produced where?
• how?
• has what significance?

Answer 11

• formed in peipheral tissues (ex: prostate) - not in the testes,
• from testosterone - by 5a-hydroxylase
• more potent than testosterone

Question 12

adrogen binding protein

• produced where?
• under what regulation?
• has what role?

Answer 12

• by sertolie cells in seminferous epitheium
• under regulation of
  
  • FSH (from GnRH)
  • testosterone (+)
• secreted into tubular lumen to bind & maintain high levels of testosterone

Question 13

summarize the roles of LH and FSH in the male.

Answer 13

• hypothalamus produces GnRH
  
  • GnRH –> acidophiles (ant pituitary)
    
    • LH –> leydig cells
      
      • testosterone
        
        • secondary sex characteristics
        • sertoli cells
          
          • ABP
    • FSH –> sertoli cells
      
      • spermatogenesis:
      • synthesis of:
        
        • ABP
        • inhibin - inhibits FSH

Question 14

how is negative feedback exerted in the male reproductive cascade?

Answer 14

by

• testosterone (from LH) inhibits production of LH
  
  • @ hypothalamus & ant pit
• inhibin (from FSH) inhibits production of FSH
  
  • @ ant pit

Question 15

estrogen synthesis?

• occurs where?
• under what regulation?
• depends on what enzyme?
• produces what products?
• that have what effects?

Answer 15

main estrogen = 17B-estradiol

• occurs in
  
  • ovarian follicles: directly from testosterone
  • peripheral tissues: from other androgens (androstenedione)
• depends on: aromatase
• under regulation: of FSH (from GnRH)
• effects:
  
  • female secondary sex characteristics (breasts, fat deposition, high pitched voice)
    
    • does aslso exist in males

Question 16

what is the role of LH in the female?

Answer 16

acts on corpus luteum to stimulate ovulation

Question 17

summarize the role of FSH and LH in female reproduction

Answer 17

• GnRH stimulates production of
  
  • FSH: acts on ovarian follicules –> estrogen production + follicular development
  • LH: acts on corpus luteum –> progesterone production

Question 18

discuss the two major phases of the menstrual cycle and

• what hormonal fluctuations they involve
• what key events they include
• how they effect the uterine lining

Answer 18

two major phases

• follicular phase
  
  • triggered by FSH,
  • acts on follicular cells to induce
    
    • follicular proliferation
    • rise in estrogen
  • endometrium grows
• luteal phase
  
  • triggered by LH, which
  • act on corpus luteam to induce
    
    • ovulation
    • rise in progesterone
  • ​endometrium grows

Question 19

during what days of the menstrual cycle does does “menses” occur?

at what age does “menses” stop?

Answer 19

• day 26-30
• age 40-45

Question 20

what is “premenstrual syndrome”

cause?

presentation?

Answer 20

• likely due to drop in estrogen and progesterone leading up to menses
• leads to:
  
  • headaches
  • mood swings
  • extreme cases: “PDD” - disrupts work / personal relationsips

Question 21

sex hormone bindings globulins (SHBG)

• from what are they derived?
• to what do they find?

Answer 21

• derived from glycoproteins (from the liver)
• bind androgens and estrogens:
  
  • androgens:
    
    • 65% bound to SHBG
    • these SHBGs are called androgen binding proteins (ABP) - made by sertoli cells - bind testosterone
  • estrogens:
    
    • 60% bound to SHBG

Question 22

androgens exist in what form in the plasma

Answer 22

• bound to proteins: 65% SHBG, 35% albumin
• free: 1-2%

Question 23

estrogens exist in what form in the plasma

Answer 23

• bound to proteins: 60% SHBG, 20% albumin
• free: 20%

Question 24

how are steroids metabolized?

Answer 24

• in the liver
• by - glucuronidation, sulfation
• does not break steroid ring

Question 25

the _placenta_ produces what hormones? what are their roles?

Answer 25

* estrogens (steroids) - maintain pregnancy * progesins (steroids) * chrorionic gonadotropin (hCG) - similar to LH * placental lactogen - similar to prolactin & GH * relaxin - _inhibits myometrial contractions_