General Overview of the Reproductive Axis Flashcards Preview

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Flashcards in General Overview of the Reproductive Axis Deck (27)
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1

Reasons why hypothalamic-pituitary axis is unique (5)

  • Male/female
  • Age-related
  • 2 pituitary hormones
  • 3 end-organ hormones
  • Also alternate hormone sources

2

Hormone profile in females: progestins, androgens, estrogens

  • Progestins
    • 10-6 g/L
    • 10-4 g/L if pregnant (excess from placenta)
  • Androgens
    • DHEA: 10-8 g/L (from adrenal source)
    • DHEAS: 10-5 g/L 
    • DHT: 0 (doesn't circulate)
    • Testosterone: 10-9 g/L (50% ovary, 50% adrenal)
  • Estrogens
    • Estrone (E1): not measured, from fat, same in males and females
    • Estradiol (E2): 10-9 g/L, 10-6 g/L if pregnant

3

Hormone profile in males: progestins, androgens, estrogens

  • Progestins
    • 10-8 g/L
  • Androgens
    • DHEA: 10-8 g/L (from adrenal source)
    • DHEAS: 10-5 g/L 
    • DHT: 0 (doesn't circulate)
    • Testosterone: 10-8 g/L (95% from testes)
  • Estrogens: 
    • Estrone (E1): not measured, from fat, same in males and females
    • Estradiol (E2): 10-9 g/L

4

Cholesterol molecule - recognize structure and correctly number carbon atoms in steroid nucleus

5

Molecules synthesized from cholesterol (6)

  • Bile salts
  • Membranes
  • Vitamin D
  • Glucocorticoids --> cortisol
  • Mineralocorticoids --> aldosterone
  • Sex steroids

6

Categories (3) and examples of sex steroids

  • Progestins
    • 21 carbons
    • Progesterone, 17-hydroxyprogesterone
  • Androgens
    • 19 carbons
    • Testosterone, DHEA, DHEA-S, adrostenedione, DHT
  • Estrogens
    • Estrone (E1)
    • Estradiol (E2)
    • Estriol (E3)

7

Key features in biosynthesis of sex steroids

  • Relies on coordinated system involving 2 cell types
  • Involves progressive reduction in number of carbon atoms
  • Various sex steroids produced in extra-gonadal tissues
    • Placenta, dermis, adrenal glands, adipose tissue

8

Rate-limiting step of sex steroid synthesis

  • Conversion of cholesterol (27 carbons) to pregnenolone (21 carbons)
  • Catalyzed by 20,22-desmolase (rate-limiting step)
  • Pregnenolone - goes on to be converted into all other sex steroids

9

3 categories of sex steroids

  • Progestins
  • Androgens
  • Estrogens

10

Progestins

  • 21-carbon sex steroids
  • Pregnenolone
  • 17-a-hydroxypregnenolone
  • Progesterone
  • 17a-hydroxyprogesterone (17-OH-P)

11

Androgens

  • 19-carbon sex steroids
  • Testosterone
  • Dehydroepiandrosterone (DHEA)
  • Dehydroepiandrosterone-sulfate (DHEA-S)
  • Dihydrotestosterone (DHT)
  • Adrostenedione
  • 5a-reductase: converts testosterone to dihydrotestosterone in target cells (prostate and skin)
    • Biologic activity of DHT 30-50x higher than testosterone

12

Estrogens

  • 18-carbon sex steroids
  • Estrone (E1)
  • Estradiol (E2)
  • Estriol (E3)
  • Aromatase: converts androgens into estrogens
    • Present in gonads & various peripheral tissues (adipose tissue, liver, CNS)

13

Hormones involved in hypothalamic-pituitary-gonadal axis (7)

  • Gonadotropin releasing hormone (GnRH)
  • Follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Androgens
  • Progestins
  • Estrogens

14

GnRH

  • Released in hypothalamus in pulsatile fashion into portal circulation, travels to anterior pituitary
  • MOA: GnRH binds to receptor on gondadotroph cell surface and stimulates FSH and LH secretion from AP

15

FSH and LH

  • Released by AP following stimulation by GnRH
  • Primary regulators of gonadal function in both sexes
  • Patterns of FSH/LH secretion change over the life cycle
  • Ovulatory women: levels of FSH and LH vary throughout menstrual cycle - reach peaks shortly before ovulation
  • Once secreted: both stimulate production of sex steroids and inhibin
  • LH stimulates rate-limiting conversion of cholesterol into pregnenolone in two ways:
    • Increasing amount of desmolase
    • Enhancing affinity of desmolase for cholesterol

16

Androgens

  • Secreted by Leydig cells in males, theca cells in females following LH stimulation
  • Males: 
    • Resulting testosterone acts on Sertoli cell to support spermatogenesis and synthesis inhibin
    • Provides negative feedback at levels of AP (decrease FSH/LH) and hypothalamus (decrease GnRH)
  • Females
    • Androgens produced by theca cells (lack aromatase) diffuse to nearby granulosa cells where they are converted into estrogens

17

Progestins

  • Secreted by theca cells and granulosa cells in women following stimulation by LH (theca cells) or FSH (granulosa cells)
  • Regulates growth and development of tissues and organs related to ovulation, menses, pregnancy, and lactation
  • Provides negative (or positive, depending on the situation) feedback on the AP (decrease FSH/LH) and the hypothalamus (decrease GnRH)

18

Estrogens

  • Secreted by granulosa cells (theca cells lack aromatase) in response to FSH stimulation
  • Regulates the functions of many tissues in the body, including those of the reproductive tract
  • Provides negative feedback at levels of AP (decrease FSH/LH) and hypothalamus (decrease GnRH)

19

Inhibins

  • Secreted by Sertoli cells in men and granulosa cells in women in response to FSH stimulation
  • Provides negative feedback at level of AP (decrease FSH/LH)

20

Primary areas of hypothalamus responsible for production of GnRH and key features of GnRH secretion

  • Originates in neurons of arcuate nucleus and preoptic area of hypothalamus
  • Released into portal circulation in pulsatile fashion
    • Pulsatility is key to physiologic stimulation of AP - Constant administration of GnRH actually suppresses pituitary response
      • Adult males: 8-14 pulses/24 hour period
      • Adult females: patterns of GnRH secretion vary throughout the menstrual cycle

21

Functions of testosterones

  • Anabolic: growth in muscle and height
  • Androgenic: development of male genitalia, spermatogenesis, secondary sex characteristics (hair, voice, acne), embryogenesis

22

Functions of female sex hormones

  • Oogenesis and ovulation
  • Puberty
  • Embryogenesis
  • Prepare for implantation
  • Breast development and lactation

23

2-cell theory of sex steroid production

  • In both sexes - gonadal sex steroid production & gametogenesis involve 2 distinct cell types working synergistically
  • In testes: Leydig and Sertoli cells
  • In ovary: theca and granulosa cells 
    • Both located at surface of ovary (ovarian cortex)
  • Both cell types required to metabolize cholesterol into estradiol
  • Male Leydig and female theca cells: interstitial cells with ability to make andorgens and inability to make estrogens due to absence of aromatase
  • Male Sertoli and female granulosa cells: immediately adjacent to developing gametes with ability to make inhibin and ability to convert androgens into estrogens due to presence of aromatase

24

Male sex steroid production

  • In response to LH
  • Leydig cells produce 95% of testosterone in males by:
    • amount of desmolase and
    • affinity of desmolase for cholesterol

25

Female sex steroid production

  • In response to LH secretion, theca cells produce progesterone and androgens
  • Theca cells lack aromatase (and therefore capacity to make estrogens)
  • Adrostenedione from theca cells must therefore diffuse into nearby granulosa cells for estrogen to be produced
  • Granulosa cells (do have aromatase) convert androstenedione into estradiol
    • Lack enzyme which converts progesterone into androgens - progesterone from granulosa cells must diffuse to theca cells --> converted into androstenedione --> then diffuse back to granulosa cells to be converted into estradiol

26

Major extra-gonadal sources of various sex steroids

  • Adrenal cortex
  • Skin
  • Adipose tissue

27

Menstrual cycle and hormone fluctuations

  • Levels of FSH and LH vary throughout the menstrual cycle, reaching peaks shortly before ovulation
  • Levels of circulating estradiol and progesterone produced in response to FSH/LH also fluctuate in cyclic pattern
  • Endometrial cells which form uterine lining respond to fluctuations in predictable pattern --> culminates in menstrual blood flow