Differential expression and regulation of estrogen receptors (ERs) in rat pituitary and cell lines:: Estrogen decreases ERα protein and estrogen responsiveness

Estrogen (E) regulates the synthesis and secretion of several pituitary hormones during the reproductive cycle in a cell- and promoter-specific manner. One mechanism underlying cell specificity is the differential expression of estrogen receptor (ER) isoforms. We used in vivo and in vitro rodent pituitary cell models to examine the expression and regulation of ER alpha, ER beta, and the pituitary-specific ERa isoform, truncated estrogen receptor product-1 (TERP-1). In cycling female rat pituitaries, ERP messenger RNA (mRNA) levels fell 40% on the morning of proestrus and were suppressed by E or dihydrotestosterone in ovariectomized females. In lactotrope and gonadotrope cell lines (GH(3), RC4B, L beta T2), progesterone (P) or P plus E also suppressed ERP. TERP-1 mRNA increased 3-fold at proestrus and in response to E treatment in vivo and in cell lines. ER alpha mRNA levels were not regulated significantly by any treatment in vivo or in cell lines. However, E suppressed ER alpha protein levels in vivo and in cell lines, and reduction of ER alpha protein levels by E or the antiestrogen ICI182,780 reduced E-stimulated transcriptional activation of the PRL promoter in GH, cells. TERP-1 and ERP protein levels were low to undetectable in cell lines, but E stimulated TERP-1. Because E treatment decreases ERP mRNA and ER alpha protein and increases levels of TERP-1 (which can suppress ER alpha/beta activity), the dynamic steroid-induced changes in ER expression in the rat pituitary during the midcycle gondaotropin/PRL surge may provide a means for ovarian steroids to limit positive feedback.