Estrogens and antiestrogens are known to have effects on protactin (PRL)-producing cells in the anterior pituitary. This study was planned to investigate the effects of estrogen and tamoxifen at immunohistochemical. and immunoelectron microscopic levels on PRL cells of female rat pituitary. Animals were divided into three groups of eight adult female rats each. The first group was the control. group. 200-mu g/day of estrogen was administered subcutaneously for 11 weeks to 16 rats. Tamoxifen was administered to eight of them for the Last 15 days. In diethylstilbestrol (DES)-induced group, serum PRL levels and pituitary weights were found to be elevated when compared with the control group. In the DES plus tamoxifen group the readings were close to that of the control group. PRL-positive cells were enlarged and strongly immunostained in DES-induced group when assessed by tight microscopy. Tamoxifen prevented this effect. At the ultrastructural. level., in the tamoxifen treated group, PRL-producing cells contained both immunopositive and immunonegative secretory granules. Numerous PRL-producing cells exhibited progressive morphological changes in the nuclei compatible with the apoptotic process. The results of this study indicate that tamoxifen prevents not only the proliferative effect of estrogen but also inhibits the secretion mechanism of the cells. (c) 2005 Elsevier GmbH. ALL rights reserved.