Is the decrease in the hypophysiotropic signal frequency normally observed during the luteal phase important for menstrual cyclicity in the primate?

The two phases of the ovulatory menstrual cycle of the primate are characterized by divergent activities of the GnRH pulse generator. During the luteal phase, LH pulse frequency is significantly reduced below that observed during the follicular phase. In this report we investigate whether the decrease in pulse frequency during the luteal phase is of physiological relevance to normal menstrual cyclicity. We have tested the effect of a pulsatile GnRH infusion given iv at hourly intervals for a period of 8-10 days during the luteal phase on the subsequent three to five cycles in eight female rhesus monkeys. Three of the eight animals received two treatment courses. Amounts of GnRH infused were 1.5 micrograms/pulse (n = 2 trials); 3.0 micrograms/pulse (n = 7); and 4.0 micrograms/pulse (n = 2). LH response to GnRH pulses of 1.5 and 3.0 micrograms resembled spontaneous LH pulses observed during the luteal phase. During the GnRH infusion period, the monkeys were fitted with a primate vest and tethered. Eleven control experiments were performed in these monkeys under similar conditions. GnRH therapy during the luteal phase affected subsequent cycles significantly, while no differences were observed in the control experiments. Overall mean follicular phase length in the control cycle was 13.4 days; it was significantly increased (P less than 0.005) in all post-GnRH treatment cycles to reach 34.4 (+/- 10.9), 43.9 (+/- 12.7), 40.4 (+/- 13.0), and 23.1 (+/- 4.8) days (+/- SE) in the first to fourth post-GnRH cycles, respectively. Progesterone secretion was significantly lower (P less than 0.05) in the first two post-GnRH cycles than in the control cycles: progesterone, 46.4 (+/- 2.1) in all control cycles, decreased to 27.7 (+/- 3.7), 24.8 (+/- 4.3), 34.0 (+/- 5.4), and 32.0 (+/- 6.5) surface units (+/- SE) from the first to fourth post-GnRH cycles, respectively, while luteal phase length remained relatively unchanged. The data indicate that significant disturbances in the menstrual cycle of the rhesus monkey follow imposed changes in the normal frequency pattern of the GnRH hypophysiotropic signal during the luteal phase and suggest that the naturally occurring slowing of GnRH-LH pulse frequency during the luteal phase is a relevant phenomenon in the sequence of events which control menstrual cyclicity.