Opiatergic Inhibition of Pulsatile Luteinizing Hormone Release during the Menstrual Cycle of Rhesus Macaques1

The endogenous opioid peptides (EOPs) may inhibit the rate of hypothalamic go-nadotropin-releasing hormone (GnRH) release and hence the frequency of pulsatile luteinizing hormone (LH) release, particularly in the luteal phase of the menstrual cycle. Our objectives were to compare the effects of an opiate antagonist, naloxone (NAL), on the patterns of LH, estradiol-17β (E2), and progesterone (P4) secretion during the follicular and luteal phases of the macaque menstrual cycle. Plasma levels of E2, P4, and bioactive LH were measured in serial, 15-min blood samples during 8-hr infusions of NAL (2 mg/hr) or saline, either on Days 5 or 6 of the follicular phase (FN and FS, n = 5 and 4, respectively) or on Days 8, 9, or 10 of the luteal phase (LN and LS, n = 5 each) of a menstrual cycle. The pulsatile parameters of each hormone were determined by PULSAR analysis and the correspondence of steroid pulses with those of LH were analyzed for each cycle stage in each animal. As expected, LH mean levels and pulse frequencies in LS monkeys were only about one-third of those values in FS animals. NAL had no effects on pulsatile LH, E2, or P4 release during the follicular phase. In contrast, luteal phase NAL infusions increased both LH mean levels and pulse frequencies to values which were indistinguishable from those in FS animals. LH pulse amplitudes did not differ among the four groups. Mean levels and pulse frequencies of P4 secretion in LS monkeys were about 4- and 14-fold greater than those values in FS animals. Mean levels and pulse amplitudes of P4 release in LN animals were greater than those values in all other groups. LH and E2 pulses were not closely correlated in follicular phase animals, and this pulse association was not altered by NAL. In FS monkeys, LH and P4 pulses were not correlated; however, NAL increased this LH-p4 pulse correspondence. LH and P4 pulses were closely correlated in luteal phase animals and this association was not affected by NAL. Our data suggest that the EOPs inhibit the frequency of pulsatile LH secretion in the presence of luteal phase levels of P4. During the midfollicular phase when LH pulses occur every 60 to 90 min, the opioid antagonist NAL alters neither the pulsatile pattern of LH release nor E2 secretion, but NAL may directly affect P4-secreting cells.