Morphological studies of prolactin-secreting cells in estrogen receptor alpha and estrogen receptor beta knockout...

Estrogens play a major role in the regulation of prolactin (PRL) secretion through activation of pituitary and hypothalamic estrogen receptors (ERs). In order to evaluate the relative role of ERalpha and ERbeta in the control of PRL density in the pituitary gland, we performed immunocytochemical localization of PRL and ERs in pituitaries of wild-type (WT), ERalpha knockout (KO) and ERbetaKO mice. In WT and ERbetaKO anterior pituitaries, the vast majority of secretory cells contained ERalpha immunoreactivity, while no ERalpha immunostaining could be found in ERalphaKO pituitaries. No ERbeta immunoreactivity could be detected in pituitaries of WT, ERalphaKO or ERbetaKO mice. At the light microscopic level, a large number of cells staining for PRL were present in pituitaries of female WT, while in female ERalphaKO pituitaries, the density of PRL cells was much lower. In WT male pituitaries, the density of PRL cells was lower than observed in female WT, while PRL staining was markedly decreased in male ERalphaKO as compared to male WT. In ERbetaKO mice of both sexes, the results were identical to those observed in WT animals. At the electron microscopic level, in WT mice of both sexes, type 1 PRL cells exhibited a well-developed Golgi apparatus and a large number of strongly stained large mature and immature secretory granules. Type 2 PRL cells were also present in the pituitary. Type 2 PRL cells contain small poorly labelled granules. In ERalphaKO mice of both sexes, type 1 PRL cells were atrophied with poorly developed Golgi apparatus, and no type 2 PRL cells could be observed. In ERalphaKO pituitaries, typical gonadectomy cells were found. No ultrastructural changes were observed in PRL cells of ERbetaKO mice. The present data strongly suggest that the positive regulation of PRL expression at the pituitary level by estrogens is mediated by ERalpha and does not involve ERbeta activation.