Hypothalamic-Pituitary-Ovarian Axis

Anatomy
Hypothalamus
 Anatomy: nuclei in the brain (located superior to optic chiasm) involved in synthesis and secretion of
releasing hormones; other functions include hunger, thirst, sleep, body temp
 Neuro-endocrine: many releasing hormones (e.g., GnRH) are released into capillaries for transport to the
anterior pituitary for downstream effects; peptide hormones are transported like neurotransmitters from
the neuronal cell body in secretory granules to the posterior pituitary
 Hormones: GnRH, TRH, CRH, GHRH, GHIH, dopamine; oxytocin, vasopressin

Anterior Pituitary (adenohypophysis)

 Anatomy: extends from hypothalamus via infundibulum (also superior to optic chiasm)
 Primarily a collection of endocrine cells that produce various hormones (LH, FSH, GH, TSH, ACTH,
prolactin)

Ovary
 Part of the female reproductive system along with uterus and fallopian tubes
 Anatomy
o Cortex: outer layer with germinal epithelium containing oocytes in follicles
o Medulla: vascular stroma containing blood vessels, lymphatics, nerves
o Hilum: attachment to ovarian ligament and ovarian artery/vein within
 Functions: (1) oogenesis, (2) production of sex hormones (e.g., estrogen, progesterone)
 Ovarian follicle made up of germ cell and surrounding endocrine cells

Hormones
Gonadotropin Releasing Hormone (GnRH)
 Decapeptide released by GnRH neurons in hypothalamus that modulates release of LH, FSH from
anterior pituitary
o pulsatile GnRH delivery (initiated at puberty) to pituitary gonadotropes stimulates sustained
gonadotropin secretion
o continuous infusion with GnRH rapidly decreases both LH and FSH secretion, an effect that is
easily reversed with a return to pulsatile stimulation
 Agonist therapy (e.g., leuprolide) can be used to treat endometriosis, leiomyomas, precocious puberty,
breast cancer, and prostate cancer

Gonadotropins
 glycosylated polypeptides with alpha, beta subunits stored in gonadotropic cells of anterior pituitary;
pulsatile GnRH binding to receptor stimulates release
o slower frequency of receptor binding favors FSH release
o faster frequency favors LH release
 Luteinizing Hormone (LH)
o Activates cholesterol desmolase in theca cells to produce androstenedione
o Rise in estradiol levels during follicular phase triggers positive feedback on rapid increase in LH
release  triggers ovulation (i.e., rupture of the dominant follicle), corpus luteum development
to maintain hormone release during the luteal phase
 Follicle-Stimulating Hormone (FSH)
 o Activates aromatase in granulosa cells to convert androgens (from theca cells) into estrogen (17-
β-estradiol), which stimulates follicular maturation
o Positive feedback loop as local estradiol enhances FSH effect on follicles

Estrogen
 Stimulates follicular maturation, endometrial growth, breast development
 more systemic effects include decreased bone resorption, LDL/HDL profile
 Estradiol most potent with estrone in post-menopausal women, estriol during pregnancy

Progesterone
 Produced by corpus luteum in the ovary, but a small amount from adrenal
 Involvement in maintaining pregnancy
o after ovulation, corpus luteum develops and produces progesterone
o fertilization increases corpus luteum progesterone until week 9-10 (luteal-placental shift)

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