Pineal-mediated inhibition of prolactin cell activity: Investigation of dopaminergic involvement.

Abstract

The purpose of these studies was to determine whether the inhibitory effects of short photoperiod exposure on prolactin cell activity in male Syrian hamsters and/or the inhibitory effects of melatonin treatment on the growth and activity of diethylstilbestrol- (DES) induced prolactinomas in Fisher 344 (F344) rats were possibly mediated through alterations in dopaminergic regulatory mechanisms. In both the hamster and the rat, changes in hypothalamic dopamine neuronal activity and changes in pituitary responsiveness to dopamine have been suggested as possible mechanisms in the prolactin-inhibitory effects of light deprivation or melatonin administration. The present studies in the male Syrian hamster addressed two issues. First, it was of interest to determine if anterior pituitaries of long photoperiod-exposed male hamsters possess dopamine receptors, which are presumably necessary for responsiveness to dopamine. This was accomplished by analysis of ³H-spiperone binding to anterior pituitary membranes. Second, possible changes in pituitary sensitivity to dopamine were assessed by comparison of dose response curves for the inhibition by dopamine of prolactin release from hemipituitaries incubated in vitro from both long and short photoperiod-exposed animals over a series of time points from three to fifteen weeks. In the second series of experiments, adult female F344 rats received daily injection of melatonin or saline vehicle. After two weeks, half of the animals were sacrificed for analysis of ³H-spiperone binding to anterior pituitary membranes, measurement of hypothalamic dopamine turnover and analysis of in vitro pituitary sensitivity to dopamine. The remaining animals received subcutaneous implants containing DES and injections were continued on the same schedule until sacrifice four weeks later for measurement of the same parameters. In both the hamster and rat models, treatments exerted profound inhibitory effects on indices of prolactin cell activity. However, these studies provide no evidence for the involvement of altered dopaminergic regulation in the production of such effects. Neither pituitary sensitivity to dopamine in vitro nor hypothalamic dopamine neuronal activity was enhanced by short photoperiod exposure or melatonin treatment. Prolactin-inhibitory effects of these treatments appear to be mediated through as yet unidentified dopamine-independent mechanisms.