Female Hormones

Question 1

GnRH Pulsation

Answer 1

• GnRH is released into portal system in pulsatile manner; pattern and frequency influences LH/FSH secretion
• Generally, 1:1 GnRH to LH ratio b/c all GnRH conc in portal circulation (so you can meas LH in serum as proxy for GnRH amounts)
• Cont GnRH will down-regulate GnRH receptors (used in precocious puberty from precocious GnRH secretion and estrogen-dep breast cancer)
• Faster GnRH pulsation = more LH than FSH
• Slower GnRH pulsation = dec LH and inc FSH
• Rate of GnRH secretion also controls amount of glycosylation of LH and FSH w/ sialic acid b/f secretion (more glycosylation = longer half-life but less potent)

Question 2

How does GnRH work at gonadotrophs?

Answer 2

-binds transmembrane receptor on gonadotrophs in anterior pituitary –> DAG/protein kinase C path –> inc intracell Ca++ –> LH/FSH secretion

Question 3

Kisspeptin

Answer 3

• Specific GnRH neuron afferent; binds GPCR on GnRH neurons so stimulate pulsatile release of GnRH
• From KISS1 gene
• Responsible for much of the feedback regulation on the reproductive system (INDIRECT)

Question 4

Kallman Syndrome

Answer 4

• failure of GnRH neurons to migrate from outside CNS to brain in embryonic development; no stimulation of pituitary (hypothalamic hypogonadism); often also have midline congenital defects

Question 5

Pos v Neg Feedback on GnRH

Answer 5

• Pos
  
  • Huge estradiol surge in late follicular phase –> massive LH/FSH surge
    
    • Acts on both hypothalamus and pituitary
    • Must be critical conc and duration of estradiol
• Neg
  
  • Inhibin only inhibits FSH at level of pituitary
  • Sex hormone receptors on kisspeptin and other GnRH afferents like opioid neurons
  • Estradiol - mainly at pituitary
  • Testosterone - mainly at hypothalamus
  • Progesterone - solely at hypothalamus (prior estradiol causes in progesterone receptors at hypothalamus to inc sensitivity)
• Stressors - psychosocial, undernutrition, strenuous exercise can all suppress GnRH secretion (can eventually lead to infertility)

Question 6

Endometrium of Proliferative Phase

Answer 6

ESTROGEN

• Estrogen causes epithelial proliferation (long glands and mitosis in epithelium and stroma)
• Glands look like purple test tubes (long section) or donuts (cross-section)

Question 7

Endometrium of Secretory Phase

Answer 7

PROGESTERONE

• Progesterone inhibits epithelial proliferation and induces secretory activity

1- Early Secretory (first half) - vacuoles expand from subnuclear to supranuclear vacuoles then secrete into gland (piano key appearance)

2- Late Secretory (second half) - max edema of stroma; prominent spiral arterioles; glands start to invaginated (corkscrew appearance); predecidualization (PINK)

Question 8

Endometrium if Menstuation

Answer 8

• withdrawal or progesterone –> collapse of endometrium

- fragmented glands, hemorrhage, thrombosis, inflammatory infiltrate (can no longer identify glands)

Question 9

Endometrium if Gestation

Answer 9

• corpus luteum (cells left in ovary) cont to create sex hormones
• Arias-Stella Reaction - hyper secretory state; enlarged endometrial glands, clear or eosinophilic cytoplasm, nuclear changes (smudged, pleomorphic)
• Decidualization - tons of progesterone –> glycogen accumulation in stromal cells; more glandular secretions and eosinophilic accumulations (PINK)
• “Decidua” = endometrium that is primed and ready for implantation

Question 10

DPE

Answer 10

Disordered Proliferative Endometrium (DPE)

• irregular bleeding NOT due to anatomic lesions or underlying medical issues
• Stuck in first half of cycle; estrogen dominant but also breakdown
• Fibrin clumps in endometrial stroma (necrosis); stromal crumbling; glands of varying sizes; mix of mitosis and blood/inflammation