Reproductive Endocrinology Flashcards
organs/brain regions and hormones associated with Hypothalamic-Pituitary-Gonadal Axis?
Hypothalamus: Gonadotropin Releasing Hormone (GnRH) Pituitary: Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH) Ovary: Estradiol Progesterone Testes: Testosterone
What is GnRH? What results from it’s activation?
10 aa peptide
Secreted in pulsatile fashion (2-3 hr cycle)
Higher frequency stimulates FSH secretion
Lower frequency stimulates LH secretion
Sexual maturity results from activation of GnRH secretion
Describe FSH and LH. What function do they play in males and females?
Heterodimeric glycoproteins
α-subunit – shared by FSH, LH, TSH, and hCG
ß-subunit – provides unique actions of hormones
FSH - MW ~34,000
LH – MW ~28,000
Each have trophic functions in males and females
Describe sexual differentiation in embryos.
Up to 8 weeks gestation, embryos contain primordial genital ducts of both sexes:
Wolffian – male
Mullerian – female
At 8 weeks, testes begin production of:
Testosterone – supports development of Wolffian:
Epididymis, vas deferens and seminal vesicles
Anti-mullerian hormone – blocks Mullerian growth:
Fallopian tubes, uterus, upper vagina
Lack of testosterone action leads to Wolffian degeneration and Mullerian development
What happens during female puberty? Adrenarche? Menarche?
~400,000 primordial follicles at puberty
300-400 will reach maturity and ovulate
Remainder “die” by atresia throughout life
Puberty:
Adrenarche – onset of adrenal androgen synthesis
Onset at 6-7 years
Androstendione, DHEA and DHEAS
Dec. sensitivity of HP axis to negative feedback
GnRH and gonadotropin secretion
Menarche – onset of menstrual cycles
Describe the Female HPG Axis.
GnRH stimulates FSH and LH release FSH – follicular maturation and estradiol synthesis LH – follicular rupture and progesterone synthesis Estradiol (E2) Endometrial proliferation Pos and neg feedback Progesterone (P4) E ndometrial support
Name two Female hormones and their functions.
Estradiol(-17ß) – E2 18 carbon aromatic steroid Promotes secondary sexual characteristics Increases HDL, some proteins (eg, TBG) Synthesized in ovary and placenta
Progesterone – P4 21 carbon steroid Precursor of many steroids Some influence on breast development Primarily involved in pregnancy
How is Estradiol measured?
Estradiol
Reference is interval age and menstrual cycle dependent
39-375 pg/mL (follicular phase)
49-440 pg/mL (luteal phase)
How is progesterone measured?
Progesterone
Ref. interval is age, cycle & pregnancy stage dependent
0-2.7 ng/mL (follicular phase)
3.0-31.4 ng/mL (luteal phase)
Pregnancy: 11.0-45.0, 26.0-89.0, 46.0-423 ng/mL by trimester
Immunoassay (competitive)
LC-MS/MS
How is Gonadotropin measured?
Immunoassay (usually sandwich assays)
Reference ranges sex, age and cycle variable
Ultrasensitive assays available – necessary for prepubertal evaluations
What happens during an LH surge?
Release of egg from follicle
What happens during the follicular phase?
Late luteal phase (of prev. cycle) E2 and P4 decline, FSH secretion increases (loss of negative feedback)
FSH stimulates follicular proliferation and E2
Day 1-4 – several follicles recruited and develop
Granulosa cells synthesize and secrete E2
Day 5-7 – dominant follicle selected, suppressing others
E2 stimulates endometrial (uterine lining) proliferation
E2 negative feedback suppresses FSH secretion
E2 synthesis continues
Antral follicle is final product
What happens during the ovulatory phase?
Rising follicular E2 stimulates LH surge at day 12-13 via positive feedback
LH peaks 24-36 hours later
Ovulation – 10-12 hrs post LH peak (day 14)
- –Follicular rupture
- –Ovum release
LH stimulates follicular synthesis of P4
Ovum captured by fallopian tubes
What happens during the luteal phase?
Ruptured follicle transforms to corpus luteum
Corpus luteum (CL) synthesizes P4 and E2
-P4 rises ~3 days post ovulation
-P4 suppresses LH and FSH secretion
-P4 peaks about 8-9 days post ovulation
Fertilized ovum implants in uterine lining
-hCG synthesis by trophoblast maintains CL
-CL P4 maintains endometrium
Without hCG, CL begins regression ~day 9
-Decreasing P4 promotes endometrial sloughing
What is menopause?
Defined as 12 months of amenorrhea
—Mean age at 51 years
—No correlation with age of menarche
Primary depletion of ovarian follicles
Decreased estradiol (10% of normal levels)
Increased FSH & LH (no negative feedback)
—FSH 10-15x due to longer half-life (4 hrs)
—LH 4-5x (half-life 30 minutes)