Effects of Estrogen-Induced Hyperprolactinemia on Endocrine and Sexual Functions in Adult Male Rats

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Abstract
Chronic estrogen treatment can lead to development of prolactin (PRL) secreting pituitary tumors. We have tested the ability of diethylstilbestrol (DES) to produce persistent hyperprolactinemia (hyperPRL) in adult male rats and examined the effects of this treatment on hypothalamic-pituitary-testicular function, adenohypophyseal structure, copulatory behavior and fertility. Silastic capsules containing approximately 5 mg DES were subcutaneously implanted into adult male CDP (F-344)/CrlBR rats and removed 15 or 20 weeks later. Extreme hyperPRL, as well as suppression of plasma LH and FSH levels, persisted after DES capsules were removed. In contrast, plasma testosterone levels increased rapidly after removal of DES capsules and reached normal levels within 4–6 weeks. Copulatory behavior was assessed on two occasions between 7 and 14 weeks after removal of the DES capsules and was found to be suppressed in DES-treated rats, as evidenced by significant increases in latencies to mount, to intromit and to ejaculate. Moreover, when the animals were placed with normal females, the interval until conception was significantly greater in DES-treated than in control males. In spite of these differences in copulatory behavior, 10 of 11 DES-treated males were fertile. At autopsy, 44 weeks after capsule implantation (i.e. 24 or 29 weeks after capsule removal), DES-treated rats had marked enlargement of the anterior pituitary, increased weights of the lateral prostate and the adrenals, increased levels of testicular hCG-binding sites, reduced concentration of dopamine and norepinephrine in the median eminence and increased concentration of LHRHin the preoptic area. DES-treated and control rats did not differ with respect to relative weights of the testes, ventral prostate and seminal vesicles and testicular testosterone production in vitro in the presence and in the absence of hCG. Immunocytochemical studies oí the adenohypophysis in a separate group of similarly treated animals revealed marked increases in the total number of parenchymal cells and in the relative proportion of mammotrophs. We conclude that chronic exposure of adult male CDF (F-344) rats to DES resulted in persistent massive mammotroph hyperplasia and that the resulting 20- to 100-fold elevation of peripheral PRL levels in these animals had little, if any, suppressive effect on testicular function, in spite of the drastic reduction in peripheral LH levels.