A neuroendocrine investigation of the inhibitory effect of prolactin on LH release

Abstract

Hyperprolactinemia (HP) is known to have an inhibitory effect on LH release. The aim of this research project was to further investigate the inhibitory mechanism(s) mediating hyperprolactinemic suppression of postcastration LH release in male rats. HP was induced by sc administration of purified ovine prolactin (oPRL) in a polyvinylpyrrolidone depot every 12 h, beginning at the time of orchidectomy (ORCH). oPRL suppressed postcastration LH release in graded, dose-dependent fashion. In contrast, shortloop autofeedback of oPRL on rat prolactin (rPRL) secreted from the in situ pituitary gland appeared regulated as a threshold response. The first significant suppression of LH secretion began in the high physiological range of plasma prolactin ({dollar}\sim{dollar}200 ng/ml) which is within the range encountered in pregnancy, pseudopregnancy and lactation in female rats. A striking finding was that this was the same dose which exerted PRL autofeedback. These data suggest that a common hypothalamic mechanism, stimulated by elevated PRL levels, may inhibit both LH and rPRL secretion. We next determined whether this dose-related suppression of mean LH levels resulted from differential, dose-related effects of oPRL on LH pulse amplitude versus pulse frequency. A smaller dose of oPRL significantly suppressed mean LH values by increasing the interpulse interval without changing pulse amplitude. Two higher doses of oPRL suppressed both LH pulse frequency and pulse amplitude. The mean maximal LH increments ({dollar}\Delta{dollar} LH) to two LHRH challenges were unaffected by oPRL indicating that the suppressive effect of oPRL was not by a direct action at the anterior pituitary gland. These data suggest that the neurons first affected by elevated PRL levels are the ones responsible for the coordinated firing of the LHRH neurons. Possible candidates for this neuronal mechanism would be the LHRH-LHRH collateral connections or other hypothalamic interneurons. We tried unsuccessfully to determine LHRH neuronal turnover by employing a recently published method using colchicine. In our hands, this method did not work for either LHRH or arginine vasopressinergic neurons. We characterized the responses of LHRH neurons to the neuroactive compounds norepinephrine (NE), epinephrine (E), bicuculline (BIC), neuropeptide Y (NPY) and N-methyl-D-aspartate (NMDA) to determine whether neurons utilizing these transmitters were involved in mediating HP suppression of LH. Third cerebroventricular administration of E and NPY and iv NMDA stimulated LH release. The mean maximal LH increments to these compounds in HP rats were suppressed. These data indicate that PRL either acts directly on the LHRH neurons to decrease their responsivity to all stimuli, and/or, that PRL acts indirectly to inhibit glutamatergic, NPYergic and adrenergic neurons that are stimulatory to LHRH release.