Estradiol Augmentation of Pituitary Responsiveness to Gonadotropin-Releasing Hormone in Women1

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Abstract
This study was designed to investigate the possibility that 17β-estradiol plays a role in the initiation of the surge of gonadotropins at midcycle by increasing pituitary responsiveness to hypothalamic gonadotropin-releasing hormone (GnRH or LRF). Seven women received 2.5 μg/kg estradiol benzoate im every 12 hr on days 1–6 of the menstrual cycle to approximate the secretory rate of estradiol by the ovary during the late follicular phase. On days 7 (7 subjects), 8 (4 subjects), and 9 (2 subjects) an iv bolus of 100 μg GnRH was administered. The mean maximal increases in serum LH (Δ max LH) of 216.9 ± 41.9 (se) and FSH (Δ max FSH) of 28.9 ± 6.4 on day 7 were significantly greater (p < 0.01) than those in a control group of women who did not receive estradiol and to whom 100 μg GnRH was administered on 1 day during the first week of the menstrual cycle (Δ max LH = 41.4 ± 4.7, Δ max FSH = 9.3 ± 1.7). The maximum LH concentrations, which occurred at 20 to 30 min following GnRH in the control group, did not occur until 90 to 120 min in the estradiol-treated group. Similarly, the mean time of the maximum FSH concentrations occurred later in the treated group (107.1 ± 14.4 min) than the control group (58.8 ± 7.1 min). While LH and FSH responses on days 8 and 9 were also greater than in the control group, the augmentative effect of estradiol appeared to decrease as the interval between the last injection ofestradiol and the administration of GnRH increased. The data demonstrate an augmentative efféct of estradiol on the pituitary responsiveness to GnRH which is not dependent upon the suppression of spontaneous release of gonadotropins nor upon a surge of gonadotropins induced by the estradiol.

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