Lecture 21: Reproduction I Flashcards
HPG axis
Kisspeptin -> hypothal. GnRH -> LH, FSH -> gonads
Testes
- Sertoli cells: nurse sperm develop.
- Leydig cells: hormone secretion
- Produce sperm in seminiferous tubules
Ovaries
- No SCs; finite follicles at birth
- Follicles = oocytes + surrounding structures
- Granulosa cells: nurses
- Theca cells: hormone secretion
GnRH release and regulation
Pulsatile GnRH stims. LH+FSH; pulsatile maintains sensitivity
GnRH regulation by:
- Cortisol inhib.
- PRL inhib.
- Leptin stim. (satiety)
- Ghrelin inhib. (hunger)
Continuous GnRH agonist antagonizes sensitivity
FSH
Stim. Sertoli cells + granulosa cells for germ cell growth; -> inhibin neg. fb regulates FSH only
LH
Stim. Leydig + Theca cells to produce steroids (A -> T in males, A -> E + P females) via aromatase
- Steroids have neg. fb on LH, GnRH
Androgens
T from Leydig/Theca cells: inhib. LH, GnRH. Stimulates internal male genitalia development.
DHT: stronger, more active form of T; target tissue 5alpha-reductase-1/2 will convert from T
Estrogens
Made via aromatase (Sertoli/granulosa cells, other tissues)
- E2 = most active form
- E1 = main male/post-menopause source
- E3 = maternal-fetal-placental unit during pregnancy
Progesterone
- Produced by corpus luteum/placenta
- Luteal phase E+P strongly inhib. GnRH
- Progestin analog in birth control
Sex steroid plasma transport
98% of sex steroids are protein-bound
T: SHBG, albumin
E2: SHBG
P: albumin, CBG (corticosteroid bind. globulin)
Androgen Binding Protein made by Sertoli cells w/ T/FSH stim. -> maintains high T around maturing sperm
Inhibins
Prod. by Sertoli/granulosa cells stim. by FSH to inhib. FSH
- Inhibin B lvl correlates w/ number of remaining follicles
- Regulates spermatogen. for males
- B > A in follicular phase, A > B in luteal phase
Turner syndrome
XO genotype: failure to develop ovaries
Klinefelter syndrome
XXY: develops as male
Sex determination
Sex-determining Region of Y encodes Teste-Determining Factor -> init. testes development
- Testes -> T + AMH (MIH) -> stim. Wolffian duct development, Mullerian duct degen.
T levels throughout development
Synth. at:
- end of 1st trimester
- minipuberty post-partum
- puberty
Triggers development of secondary sex characteristics
E levels throughout development
Synth. at:
- end of 1st trimester
- post-partum
- no rise until puberty; gonadostat reset
Gonadostat reset
Marks beginning of puberty. Hypothal. sensitivity to E fb inhib. drops, allowing resumption of FSH, LH pulses
Pubertal events
“BAGM”
1. Thelarche (breast develop.)
2. Pubarche (axillary/pubic hair)
3. Menarche (1st menstruation)
Estrogen/androgen roles in puberty
E -> long bone growth; high levels -> epiphyseal plate closure
A -> adrenarche increase from adrenals -> early growth spurt, sebaceous oil production, init. hair growth
Androgen Insensitivity Syndrome
- Due to lack of functional receptors, but Y chr. works
- No neg. fb to T -> increased LH, T, E
- Peripheral aromatization -> female phenotype w/ XY
- No Mullerian or Wolffian ducts
5alpha-reductase-2 deficiency
Aka “penis at 12”
- XY geno. w/ init. female pheno. then male at puberty
- Non-func. Mx in 5alpha-reductase-2 -> no DHT from T -> no ext. male genitalia
- At puberty, very high T + 5alpha-reductase-1 makes enough DHT
Congenital Adrenal Hyperplasia
- XX: masculinization (intersex)
- XY: precocious puberty
- Due to adrenal androgen hyperproduction; 21-hydroxylase or 11beta-hydroxylase deficit
- Less cortisol/aldo. -> more ACTH -> precursors redirected to DHEA, androstenedione
Spermatogenesis
Process of development from 2n spermatogonium to 1n spermatozoa; takes ~2 months
Blood-testis barrier
Formed from tight junctions giving immune privilege protecting sperm (1n = foreign genotype)
