Hypothalamic-Pituitary-Ovarian Axis

The hypothalamic-pituitary-ovarian (HPO) axis is a timed feedback system rather than a one-way hormone chain. Hypothalamic neurons release gonadotropin-releasing hormone (GnRH) in pulses into the hypothalamic-hypophyseal portal circulation. The anterior pituitary responds by releasing follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which act on the ovary. GnRH pulsatility is obligatory. Continuous GnRH exposure does not produce continuous stimulation; instead, it downregulates pituitary GnRH receptors and suppresses FSH and LH secretion. Pulse frequency also carries information. Slower pulses favour FSH, whereas faster pulses favour LH. This helps explain why altered pulse patterns produce different reproductive phenotypes rather than a simple “high hormone” or “low hormone” state. FSH supports follicular development and granulosa-cell activity. LH stimulates theca-cell androgen production, contributes to steroidogenesis, and later supports ovulation and corpus luteum function. Developing follicles produce estradiol and inhibin. Inhibin selectively reduces pituitary FSH secretion, helping the dominant follicle emerge from the group. For most of the cycle, estradiol exerts negative feedback on both the hypothalamus and pituitary. Late in the follicular phase, sustained high estradiol from the dominant follicle reverses that relationship. Positive feedback...