FREQUENCY-MODULATION OF FOLLICLE-STIMULATING-HORMONE (FSH) DURING THELUTEAL-FOLLICULAR TRANSITION - EVIDENCE FOR FSH CONTROL OF INHIBIN-B IN NORMAL WOMEN

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 d uring the luteal-follicular transition, exogenous GnRH was administere d to GnRH-deficient women using one of two regimens, and the results w ere compared to those in normal women. In the GnRH-deficient women, th e 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 wo men (physiological frequency transition; n = 8 studies) or the GnRH pu lse frequency was kept constant at a late luteal phase frequency of ev ery 4 h through the first 6 days of the subsequent early follicular ph ase of cycle 2 (slow frequency transition: n = 6 studies). The differe ntial rise in FSH secretion induced in these studies allowed us to exa mine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicul ar transition resulted in a rise in FSH and inhibin B levels that did not differ from that in nor mal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnR H for 6 days into the subsequent early follicular phase produced FSH l evels 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 us. 16.4 +/- 1.4 IU/L for the slow and physiological trans ition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associate d 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 e stradiol 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 us. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition gr oup. In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the F SH rise that initiates folliculogenesis. Alteration of FSH dynamics in duced by changes in GnRH pulse frequency in GnRH-deficient women provi des evidence that FSH stimulates inhibin B production in the human. Ti mely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH du ring the luteal-follicular transition.