Effects of Tamoxifen on Serum Prolactin Levels, Pituitary Immunoreactive Prolactin Cells and Uterine Growth in Estradiol-Treated Ovariectomized Rats

Pituitary effects of the antiestrogen tamoxifen are not well established, although estrogen is known to have a stimulatory role in prolactin secretion. Effects of tamoxifen on serum prolactin levels, pituitary wet weight and number of prolactin cells were studied. Ovariectomized female Wistar rats were injected, subcutaneously, with estradiol valerate, 50 or 300 micrograms/rat per week for 2 or 10 weeks. Tamoxifen was injected during the last days of estrogen treatment. Data were compared with two other groups, treated with estradiol valerate alone or estradiol valerate plus the dopamine agonist bromocriptine. Serum prolactin levels were increased by estrogen treatment with all doses used. Furthermore, rats treated with 300 micrograms of estradiol valerate, for 2 and 10 weeks, showed a clear increase in pituitary weight and number of prolactin cells (p < 0.05). Bromocriptine decreased prolactin levels, pituitary weight and the number of prolactin cells (p < 0.05). Tamoxifen associated to subacute period of estrogen administration resulted in a significant reduction of serum prolactin levels and pituitary weight (p < 0.05). No effects on prolactin levels or number of prolatin cells were observed with tamoxifen associated to chronic estrogen treatment. Tamoxifen also presented a dose-related inhibitory effect upon estrogen-stimulated rises in uterine weight and DNA content. In conclusion, the results of the present paper showed that tamoxifen reduced estrogen-stimulated prolactin levels in some, but not in other hormonal conditions and that these effects were not mediated by an inhibition of lactotroph cell growth. Further studies are needed to define the exact role of antiestrogens at molecular level in hyperprolactinemic states and their eventual connection with dopamine and its agonists.