Is the Decrease in the Hypophysiotropic Signal Frequency Normally Observed during the Luteal Phase Important for Menstrual Cyclicity in the Primate?*

Abstract

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.

Maturation of Sleep–Wake Gonadotrophin‐Releasing Hormone Secretion Across Puberty in Girls: Potential Mechanisms and Relevance to the Pathogenesis of Polycystic Ovary Syndrome

“…Importantly, low GnRH pulse frequency during the luteal phase appears to be physiologically relevant for the maintenance of long‐term cyclicity. For example, in monkeys, administration of hourly GnRH pulses during the luteal phase increased follicular phase length and decreased luteal progesterone production in the subsequent three to five cycles (15). Low GnRH pulse frequencies during the luteal phase may be important to increase FSH synthesis for later release during the luteal–follicular transition (16).…”

Comparison of the Duration of Action of Nalmefene and Naloxone on the Hypothalamic-Pituitary Axis of the Rhesus Monkey

“…In contrast, naloxone at all pretreatment intervals failed to block morphine's effect. We conclude that a single 10 mg bolus injection of nalmefene exerts significant activity at the opiate receptors that mediate the effects of morphine on LH and PRL release for at least 24 h after administration, whereas the same dose of naloxone has a duration of action less than 12 h. Based on this finding it is likely that the effects of endogenous opioid peptides in the rhesus monkey can be chronically antagonized by the daily administration of nalmefene.Endogenous opioid peptides are thought to be hypotha lamic neuromodulators of anterior pituitary hormone secre tion 11,2,4,13,16,18,25]. Evidence is particularly compel ling that endogenous opioids act as tonic inhibitors of lu teinizing hormone (LH) secretion and function as stimu latory neuromodulators of prolactin (PRL) release.…”

Effects of chronic opioid antagonism on gonadotrophin and ovarian sex steroid secretion during the luteal phase

“…(1984 ) noted prolonged intervals of LH pulses until ovulatory cycles were restored when Rhesus monkeys received hourly pulses of GnRH in the luteal phase of their cycles. Moreover, an hourly LH pulsatility during the luteal phase significantly disturbs the menstrual regularity in subhuman primates ( Lam & Ferin, 1987).…”