Effects of N-methyl-d,l-aspartate on Beta-endorphin and prolactin secretion in rams exposed to long or short days

Abstract In a previous study we demonstrated that the injection of the excitatory amino-acid N-methyl-D, L-aspartate (NMDA) stimulates an acute increase in the peripheral blood concentrations of luteinizing hormone in Soay rams, and this response varies with the photoperiodically-induced reproductive cycle. To extend these observations, we have now measured the changes in the blood concentrations of beta-endorphin and prolactin in the same animals to establish whether NMDA stimulates the secretion of other pituitary hormones. Groups of adult Soay rams were exposed to alternating 16-weekly periods of long and short days to induce a long-term cycle in the endogenous secretion of beta-endorphin (maximum under short days) and prolactin (maximum under long days). NMDA injected intravenously caused a dose-dependent increase in the blood plasma concentrations of beta-endorphin (over the range 1 to 20 mg/kg NMDA). The initial increase in beta-endorphin occurred within 2 to 4 min with peak levels after 20 to 100 min. The magnitude of the beta-endorphin response was greatest following exposure to long days when the endogenous secretion of beta-endorphin was low, while the duration of the response was greatest following exposure to short days when the endogenous secretion of beta-endorphin was high. NMDA injected intravenously also caused a dose-dependent increase in the blood plasma concentrations of prolactin but this only occurred following exposure to long days when the endogenous secretion of prolactin was high. At this time the initial increase in prolactin concentrations occurred within 2 to 4 min after the injection of NMDA as for beta-endorphin but the values continued to increase for 2 to 4 h. In a separate experiment, it was shown that pretreatment of the rams with dexamethasone (synthetic glucocorticoid, 133.4 mug/kg iv) blocked the beta-endorphin response to NMDA but had no effect on the prolactin response. This indicates that NMDA stimulates the secretion of beta-endorphin from the corticotrophs probably acting centrally to induce the release of corticotrophin-releasing hormone and/or arginine vasopressin, while NMDA acts through separate mechanisms to affect the secretion of prolactin. The overall results show that NMDA can be used as a probe to investigate the neuroendocrine control of beta-endorphin and prolactin in addition to luteinizing hormone as described previously. The multiple responses are likely to represent the effects of NMDA acting on the hypothalamus to induce the acute release of peptides and other hormones into the pituitary portal blood system to affect the corticotrophs, lactotrophs and gonadotrophs. The variation in responsiveness to NMDA related to the photoperiodic cycle may reflect changes in the synthesis and storage of the hypothalamic hormones and the influence of other neural systems. Alternatively, the changes in the secretion of endogenous excitatory amino-acids and NMDA receptors may constitute part of the neuroendocrine mechanism relaying the effects of photoperiod.