We are studying mechanisms involved in the regulation of testicular function by hormones of the anterior pituitary. In particular, we are interested in elucidating the role of prolactin (PRL) in the control of the synthesis of androgenic steroids by the testis. Prolactin is known to bind to Leydig cells in several species and to increase the number of testicular LH receptors. Evidence available to date indicates that PRL regulates also the number of its own receptors and that the nature of this regulation may be quite different in different species. We will examine the regulation of testicular PRL receptors in three spcies of laboratory animals and evaluate the functional signficance of the observed changes in PRL binding. This will be accomplished by relating changes in the number of PRL receptors in the testis to the ability of PRL to increase the number of LH receptors and to affect the content of esterified and free cholesterol and the activity of cholesterol ester hydrolase in the testis. In a separate series of experiments, we will examine the suspected role of PRL in mediating the effects of photoperiod on the susceptibility of gonadotropin release to feedback inhibition by testicular steroids. We already have evidence that experimental elevation of peripheral PRL levels can alter the ability of testosterone to suppress LH and FSH release. Changes in feedback sensitivity have been shown by other workers to play a pivotal role in naturally occurring reversible suppression of gonadal function and fertility in seasonal breeders. We will attempt to define the mechanism(s) of PRL action on steroid feedback by studies involving central nervous system lesions, pinealectomy and measurement of levels and turnover rates of neurotransmitters in different brain areas. For these studies we will utilize golden hamsters, in which peripheral PRL levels can be suppressed by exposure to a short photoperiod, and mice, in which two mutations cause congenital PRL deficiency. The results of the proposed studies will advance the understanding of mechanisms by which PRL modulates testicular and pituitary function. Since PRL is believed to influence the testis in the human male, our findings should have relevance to understanding of the function of the hypothalamic-pituitary-testicular axis in men in health and in disease.
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