In the LH surge that triggers ovulation, which POSITIVE feedback mechanism drives the preovulatory estrogen surge to stimulate gonadotroph LH release (instead of the usual negative feedback)?

• A Progesterone from the developing follicle primes the pituitary to respond to GnRH with an LH surge
• B Inhibin B from the dominant follicle paradoxically stimulates LH release at ovulation
• C Sustained high estradiol (>200 pg/mL for >48 hours) from the dominant follicle switches gonadotroph response from inhibition to stimulation — upregulating GnRH receptors and directly stimulating LH synthesis/release — the 'E2 positive feedback' ✓
• D Falling FSH removes tonic inhibition of GnRH pulse generator, causing an LH surge

Explanation

Throughout the follicular phase, rising estradiol from the dominant follicle exerts negative feedback on LH/FSH. However, when estradiol exceeds ~200 pg/mL for at least 48–50 hours, a switch to positive feedback occurs: the anterior pituitary (and hypothalamus) respond to this sustained high-estrogen signal by upregulating GnRH receptors on gonadotrophs and increasing GnRH sensitivity, directly stimulating LH synthesis and release — producing the preovulatory LH surge. This estrogenic positive feedback is a unique property of the gonadotroph occurring mid-cycle. Progesterone does amplify the LH surge once secreted, but the initiating positive feedback is estrogen-mediated. Inhibin B suppresses FSH, not LH.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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