Hyperprolactinemia-Induced Precocious Puberty in the Female Rat: Ovarian Site of Action*

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Abstract
Hyperprolactinemia induced in immature female rats by chronic treatment with sulpiride, a dopaminergic receptor blocker, resulted in advancement of the onset of puberty. While serum PRL [prolactin] levels increased promptly after initiation of the treatment and remained elevated throughout the entire period studied (day 22 to 1st diestrus after vaginal opening), gonadotropin levels did not appear to be altered and increased abruptly only at the time of the 1st preovulatory surge. Except for a decrease during the 1st diestrus, serum TSH [thyroid stimulating hormone] and GH [growth hormone] were not consistently altered by sulpiride. After 5 days of treatment, serum progesterone levels, but not those of androgens, were increased in hyperprolactinemic (HP) rats. Uterine wt, taken as an index of estrogen secretion, was unambiguously increased in HP rats, the 1st significant difference being observed 5 days after initiation of the sulpiride treatment (day 27). Ovarian estrogen and progesterone responsiveness of normal animals to gonadotropins, as determined by in vitro release of the steroids after incubation with hCG [human chorionic gonadotropin] increased with age. The response was dramatically enhanced in HP rats, its magnitude increasing markedly as the animals approached puberty. Androgen response to hCG was, however, similar in HP and control rats. In vitro release of adrenal progesterone, but not that of estrogen or androgens, was slightly enhanced in HP rats. When sulpiride treatment was terminated on the 1st day of diestrus after vaginal opening, the animals continued to show estrous cycles. By contrast, maintenance of the treatment for several days after vaginal opening resulted in a condition of constant diestrus. Apparently one of the mechanisms by which PRL induces precocious puberty in the female rat is by sensitizing the ovaries to the low circulating gonadotropin levels observed during the prepubertal period. In addition, PRL also seems to stimulate progesterone secretion by the adrenal glands.