Cellular Distribution and Gene Regulation of Estrogen Receptors and in the Rat Pituitary Gland

The pituitary gland is a heterogeneous tissue comprised of several hormone secreting and supporting cells, most of which are targeted by estrogens. Estrogen-induced changes in the pituitary are presumably mediated via the classical estrogen receptor, ERα. However, a novel receptor, ERβ, and pituitary-specific truncated estrogen receptor products (TERPs) were recently identified. The objectives of this study were to examine the distribution of these receptors in the rat pituitary and compare their regulation by estradiol in Sprague-Dawley and the estrogen-sensitive Fischer 344 rats. Pituitary cryosections were subjected to immunocytochemistry for specific cell types, followed by in situ hybridization for ERα or ERβ. ERα was expressed by approximately 45% of the lactotrophs and melanotrophs, 35% of the corticotrophs and folliculo-stellate cells, and 25% of the gonadotrophs. The expression of ERβ showed a similar pattern but was generally lower than ERα. In two cell types, melanotrophs and gonadotrophs, ERβ expression was significantly lower than ERα. In the second experiment, pituitary sections were immunostained for ERα, followed by in situ hybridization for ERβ. Only a minute population (6–10%) of either anterior or intermediate lobe cells coexpressed ERα and ERβ. In the next experiment, Fischer 344 and Sprague-Dawley rats were injected with oil or estradiol for 24 h. Total RNA from dissected anterior and posterior (neurointermediate) pituitaries was subjected to RT-PCR for ERα, ERβ, or TERPs. Interestingly, ERα and ERβ were unchanged by estradiol in either lobe of the pituitary. In contrast, estradiol increased pituitary TERP messenger RNA levels 4- to 7-fold. A 20-kDa TERP protein was detected by Western blots in the pituitary but not the uterus. There were no differences in the estradiol-induced expression of any of the receptors between the two strains of rats. We conclude that: 1) ERβ is expressed in all anterior and intermediate lobe cell types examined, albeit at a lower level than ERα; 2) no more than 10% of pituitary cells coexpress ERα and ERβ; and 3) estradiol markedly increases TERP messenger RNA levels but does not alter the expression of ERα or ERβ. We propose that estrogen receptor heterogeneity contributes to the diversity of pituitary cell responsiveness to estrogens.