HYPERPROLACTINEMIA SUPPRESSES THE LUTEINIZING-HORMONE RESPONSES TO N-METHYL-D-ASPARTATE, EPINEPHRINE, AND NEUROPEPTIDE-Y IN MALE-RATS

This study characterizes the responses of LHRH neurons to N-Methyl-D-aspartate (NMDA), norepinephrine, epinephrine (E), and neuropeptide-Y (NPY), as evidenced indirectly by the measurement of circulating LH titers, and investigates whether neurons using these compounds as neurotransmitters might be involved in mediating hyperprolactinemic (HP) suppression of LH release. Male rats were orchidectomized, adrenalectomized, and implanted with a testosterone-containing Silastic capsule, a 50% corticosterone pellet, and third cerebroventricular and right atrial cannulae at time zero. Rats received sc injections of ovine PRL (2400 mug/250 mul) in a polyvinylpyrrolidone depot or vehicle every 12 h for 48 h when experiments were performed. The mean maximal LH increments (DELTALH) in response to two doses of LHRH (0.4 and 0.8 ng/100 g BW) were not altered in HP rats, indicating that ovine PRL did not cause a change in pituitary responsiveness. NMDA (20 mg/kg BW, iv)-induced LH release peaked 5 min after injection. The DELTALH (0-5 min) in HP rats was suppressed by 53% compared with the control value. Epinephrine [5, 10, and 15 mug/2 mul, intracerebroventricularly (icv)], but not norepinephrine (20 and 40 mug/2 mul, icv), produced dose-dependent LH responses that peaked at 10 min. The DELTALH (0-10 min) in HP rats in response to 10 mug/2 mul E was suppressed by 68% compared with the control value. Two doses of NPY (2 and 10 mug/2 mul, icv) produced dose-dependent LH increments that peaked at 10 min. In HP rats, the DELTALH (0-10 min) in response to 10 mug/2 mul NPY was suppressed 52% compared with the control value. The combined administration of E (10 or 16 mug) and NPY (5 or 10 mug) produced mean maximal LH responses that significantly exceeded the additive responses of these compounds individually. This synergistic effect may be mediated by separate adrenergic and NPYergic afferents to the LHRH neurons or may, in fact, reflect corelease of these two neurotransmitters from the same neurons. The LH responses to NMDA, E, and NPY were all inhibited in HP rats. This suggests that elevated PRL levels act on the LHRH neurons, either directly or indirectly through an inhibitory afferent neuronal system, to decrease their responsivity to all stimuli.