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Frequency Modulation of Follicle-Stimulating Hormone (FSH) during the Luteal-Follicular Transition: Evidence for FSH Control of Inhibin B in Normal Women¹

The National Center for Infertility Research and the Reproductive Endocrine Sciences Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; and the Department of Pathology and Laboratory Medicine, Women and Infants’ Hospital of Rhode Island (G.M.L.-M.), Providence, Rhode Island 02905

Address all correspondence and requests for reprints to: Dr. Corrine K. Welt, National Center for Infertility Research and the Reproductive Endocrine Sciences Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.

To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition; n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion.

A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in normal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 ± 1.0 vs. 16.4 ± 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 ± 21.5 vs. 140.0 ± 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 ± 0.9 vs. day 5.6 ± 0.1; P < 0.02), and a longer follicular phase length (16.0 ± 1.4 vs. 11.6 ± 0.9 days; P < 0.05) compared with those in the physiological transition group.

In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the FSH rise that initiates folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B production in the human. Timely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH during the luteal-follicular transition.

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