EVIDENCE FOR AN ALTERED LUTEINIZING-HORMONE SENSITIVITY TO NALOXONE IN PATHOLOGICAL HYPERPROLACTINEMIA

OBJECTIVE The underlying mechanisms involved in the pathogenesis of am enorrhoea in hyperprolactinaemic states still remain unclear. Conflict ing information exists on the role of endogenous opiates on gonadotrop hin disturbances in this pathological condition. In this study we have undertaken a detailed investigation of LH and PRL secretion before an d during administration of naloxone, an opioid receptor blocker, in hy perprolactinaemic women with or without ovarian function in order to a ssess the role of ovarian steroids upon naloxone induced LH and PRL re lease. DESIGN Five anovulatory and six ovulatory subjects with hyperpr olactinaemia were studied before and during naloxone infusion. Five no rmo-prolactinaemic ovulatory subjects were included as controls. All o vulatory subjects were studied during the luteal phase of a menstrual cycle. Blood was sampled every 10-20 minutes over a Is-hour period on two alternate days. On study day I (control day), subjects received tw o sets of saline infusion every 6 hours and one saline bolus at the be ginning of the seventh hour; on study day 3 (naloxone day), they recei ved a saline infusion during the first 6 hours, an intravenous bolus o f naloxone (20 mg) at the beginning of the seventh hour and then a con tinuous naloxone infusion (1.6 mg/hour) during the ensuing 6 hours. Pi tuitary LH responsiveness and reserve were assessed on both study days by the subsequent administration of 5 and 95 mu g of GnRH 4 hours bef ore the completion of each sampling period. MEASUREMENTS Serum concent rations of LH, PRL, oestradiol and progesterone were determined by rad ioimmunoassay. LH and PRL pulse detection and characteristics were ana lysed by the Cluster program. RESULTS Serum PRL levels in hyperprolact inaemic anovulatory and ovulatory subjects were significantly elevated above the normal range. Oestradiol and progesterone serum levels duri ng the luteal phase in women with hyperprolactinaemia and regular mens es were similar to those in control ovulatory subjects. Mean LH concen trations increased during naloxone infusion (P < 0.05) in ovulatory hy perprolactinaemia and controls, whereas PRL increased (P < 0.05) only in the group of control subjects. LH pulse amplitude and pulse interva l were increased by naloxone (P < 0.05) in all the ovulatory subjects, with no significant changes in anovulatory hyperprolactinaemic women. PRL pulse characteristics were modified significantly by naloxone onl y in the control group. On day 1, GnRH administration increased LH in all groups, whereas a consistently lower pituitary LH response was obs erved after naloxone (day 3). Serum PRL levels significantly increased after GnRH administration on day 1 only in normal women, whilst on da y 3 this GnRH-dependent PRL releasing effect was significantly attenua ted. CONCLUSIONS The absence of stimulatory effects of naloxone on LH in anovulatory hyperprolactinaemia implies that endogenous opiates do not play a significant role in the mechanisms governing hypothalamic a menorrhoea in this syndrome. The results in subjects with ovulatory hy perprolactinaemia suggest the existence of an active role of ovarian s teroids on naloxone induced LH release. These data, along with those p reviously reported in normal women throughout the menstrual cycle, are consistent with the concept that sex steroid hormones contribute to t he underlying mechanisms involved in the opioidergic control of LH and PRL release. Whether PRL by itself or through other non-opioid neuroe ndocrine pathways alters the hypothalamic-gonadotroph unit still requi res further investigation.