Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

Abstract

In the present study, we evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E2 (PGE2) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O2-5% CO2. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 microM. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 microM norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE2 (2.8 microM) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE2 released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE2-induced release of LHRH. Additionally, Pb did not alter basal PGE2 release; however, it significantly blocked the NE-induced release of PGE2. Since NE-induced LHRH release is mediated by PGE2, these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE2 synthesis/release within the ME, resulting in diminished LHRH secretion.