Hypogonadism and infertility are frequent complications of prolactin pituitary tumors, the most prevalent pituitary tumor in man. Although hyperprolactinemia and its association with hypogonadism has been studied in both man and several animal models, its direct effect on testicular function, especially spermatogenesis, is poorly understood and insufficiently studied. Our proposed project is designed to study the role of elevated prolactin in disrupted reproductive/fertility potential in the rat with special emphasis on testis morphology and spermatogenesis. We have described in the hyperprolactinemic Wistar-Furth rat altered testicular morphology, not unlike that seen in the hyperprolactinemic man, which appears reversible following normalization of serum prolactin. Proposed studies in this animal model will include specific radioimmunoassays of serum testosterone, dihydrotestosterone, PRL, luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and androgen-binding protein (ABP). Testicular and epididymal ABP will be measured, daily sperm production will be determined, and perfused-fixed testes will be structurally analysed by light and electron microscopy. Sexual behavior in rats with females of proven fertility also will be studied including semen verification by daily vaginal smears. The direct effect of PRL will be evaluated in control experiments by manipulating testosterone, PRL and GH levels independantly. Reversibility of structural, endocrine and behavioral parameters found to be associated with the hyperprolactinemic state will be investigated in the post-tumor ressected rat. This project is directed at determining the effects of hyperprolactinemia on spermatogenesis and fertility in the male rat with four major objectives: 1) to clearly identify structural, hormonal and behavioral abnormalities associated with hyperprolactinemic hypogonadism; 2) to determine the magnitude and/or length of exposure of excess prolactin on reproductive function; 3) to test the hypothesis that hyperprolactinemia directly affects the gonads (both Leydig and Sertoli cell function), and; 4) to investigate the potential for complete recovery of reproductive function once prolactin is normalized. We anticipate that these studies will provide needed information about the effects of excess prolactin on reproductive dysfunction in males and further clarify normal regulatory mechanisms of testicular function.
