The effects of prolonged opiodergic blockade on LH pulsatile secretion during the menstrual cycle

Abstract

Although considerable evidence points towards a pivotal role for the endogenous opioid peptides (EOP) in the neuroendocrine regulation of GnRH-LH secretion, the effects of prolonged opioidergic blockade on LH pulsatile activity during the menstrual cycle have not been thoroughly investigated. Accordingly, 10 women in the early follicular phase (EFP, days 3 and 4), 10 women in the late follicular phase (LFP, days 9 to 13) and 7 women in the midluteal phase (MLP, days 6 to 8 after LH surge) were studied on two consecutive days before and during opioidergic blockade imposed by an opiate receptor antagonist, naloxone. Blood samples were obtained at 15 min intervals for 8 h during saline (150 mmol/l at 50 ml/h) or naloxone (30μg/kg/h) infusions. Furthermore, sequential 24-h infusions of saline or naloxone (30 μg/kg/h) were performed in 6 other women (two each in the EFP, LFP, and MLP). LH hormone series were analyzed for significant pulses by the Cluster pulse algorithm. While 8-h naloxone infusions did not change any of the LH pulse characteristics (frequency, amplitude, transverse mean, duration) in the EFP, they elevated significantly (p < 0.05) the LH pulse frequencies, pulse amplitudes and transverse mean levels in the LFP. In the MLP, the LH pulse amplitudes were significantly (p < 0.05) increased, but pulse frequencies and transverse mean levels remained unchanged. While the 24-h naloxone infusions did not alter any of the pulse characteristics in the EFP, they elicited a robust increase in LH pulsatile activity in the LFP, composed of a progressive rise in LH pulse amplitudes and transverse mean levels. The LH pulse frequencies remained unchanged. Although the 24-h naloxone infusions increased the LH pulse frequency in the MLP, they tended to decrease the LH pulse amplitude, so that the LH transverse mean levels remained unaltered. The LH pulse durations during naloxone infusions were not different from the control conditions in either phase of the cycle. These observations confirm that the effects of prolonged opioidergic blockade on LH secretion vary during the menstrual cycle, dependent on the prevailing ovarian steroid milieu. Our findings further demonstrate that a prolonged opiate blockade exerts different on LH pulse frequency, pulse amplitude and transverse mean levels during the menstrual cycle. Thus, it may be inferred that endogenous opioid peptides are variously involved in the regulation of LH pulsatile activity during the menstrual cycle.