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 < 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 ~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.