Endogenous opiates regulate the nocturnal reduction in luteinizing hormone pulse frequency during the luteal phase of the macaque menstrual cycle

Twenty-four-hour pulsatile patterns of bioactive luteinizing hormone (LH) and immunoactive estradiol (E2) and progesterone (P4) were measured during the mid-follicular (FP, Days 5, 6, or 7) and mid-luteal (LP, Days 7, 8, 9, or 10) phases of the menstrual cycle in six intact and in four ovariectomized (OVX) rhesus monkeys. Blood samples were collected remotely at 7.5-min (FP) and 15-min (LP, OVX) intervals via catheters in freely moving, vested monkeys. Hormonal patterns were analyzed by the MUNRO computer program. A significant coupling of LH and E2 pulses was observed during the FP and between the LH and P4 pulses during the LP. No diurnal rhythm of LH pulse frequency was observed during the FP or in OVX monkeys. In contrast, day/night differences in frequency were seen during the luteal phases (0.35 +/- 0.03 vs. 0.24 +/- 0.05 pulses/h, day vs. night, p less than 0.05). Naloxone (NAL), an opiate antagonist, was continuously infused (2 mg/h.i.v.) for 12 h at night during the LP. NAL treatment increased nighttime LH pulse frequency to 0.33 +/- 0.07 pulses/h, which was not different from the daytime LH pulse frequency, thereby abolishing the normal diurnal pattern. Interestingly, NAL treatment did not achieve the approximately 1 pulse/h frequency seen in the FP or OVX condition. These results support the hypothesis that P4 modulates the activity of an opioid system that is responsible both for a slowing of LH pulse frequency during the LP and for an additional nightly reduction in hypothalamic LH pulse-generating activity.