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Human Body Study

HPG Axis — Hypothalamic–Pituitary–Gonadal

The HPG axis The hypothalamus releases pulsatile GnRH, which stimulates the anterior pituitary to release LH and FSH. These act on the testes (producing testosterone and sperm) and ovaries (producing estrogen, progesterone, and oocytes). Sex steroids and inhibin exert negative feedback on both the pituitary and the hypothalamus; sustained high estrogen in the late follicular phase is the exception, triggering the ovulatory LH surge by positive feedback. Hypothalamus arcuate nucleus · KNDy neurons Anterior pituitary gonadotrophs Testes Leydig + Sertoli cells Ovaries theca + granulosa cells Testosterone · spermatogenesis virilisation · libido bone & muscle mass Estrogen · progesterone · ova menstrual cycle · ovulation pregnancy support GnRH (pulsatile) LH + FSH testosterone · sperm estrogen · progesterone sex steroids + inhibin − − Positive-feedback exception: sustained high estrogen (late follicular) → LH surge → ovulation. Solid arrows: stimulation. Dashed red: negative feedback. Continuous (non-pulsatile) GnRH shuts the axis down.

Signaling chain

Section titled “Signaling chain”

GnRH (hypothalamus, released in pulses) → LH and FSH (anterior pituitary gonadotrophs) → sex steroids and gametes (testes: testosterone, sperm; ovaries: estrogen, progesterone, oocytes).

Function

Section titled “Function”

Governs reproduction, sexual development, and secondary sex characteristics. In males, LH drives Leydig-cell testosterone; FSH supports Sertoli cells and spermatogenesis. In females, FSH/LH orchestrate the menstrual cycle — follicular growth, the mid-cycle LH surge triggering ovulation, and corpus luteum progesterone.

Feedback

Section titled “Feedback”

Predominantly negative: sex steroids and inhibin suppress GnRH/LH/FSH. A unique positive feedback exception — sustained high estrogen late in the follicular phase triggers the ovulatory LH surge. Pulsatility is essential: continuous (non-pulsatile) GnRH desensitizes the pituitary and shuts the axis down — the mechanism exploited by GnRH agonists.

Clinical relevance

Section titled “Clinical relevance”
  • Hypogonadism — primary (gonadal failure, high LH/FSH) vs. central (low LH/FSH).
  • PCOS, amenorrhea, infertility, precocious or delayed puberty.
  • Suppressed by stress, undernutrition, hyperprolactinemia, and the HPA axis.
  • Pharmacologic targets: GnRH agonists/antagonists (prostate cancer, endometriosis, IVF).

Key labs

Section titled “Key labs”

LH, FSH, testosterone, estradiol, progesterone, prolactin, SHBG, AMH.