Differential expression and regulation of estrogen receptors (ERs) in rat pituitary and cell lines: estrogen decreases ERalpha 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 ERalpha, ERbeta, and the pituitary-specific ERalpha isoform, truncated estrogen receptor product-1 (TERP-1). In cycling female rat pituitaries, ERbeta 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 (GH3, RC4B, LbetaT2), progesterone (P) or P plus E also suppressed ERbeta. TERP-1 mRNA increased 3-fold at proestrus and in response to E treatment in vivo and in cell lines. ERalpha mRNA levels were not regulated significantly by any treatment in vivo or in cell lines. However, E suppressed ERalpha protein levels in vivo and in cell lines, and reduction of ERalpha protein levels by E or the antiestrogen ICI182,780 reduced E-stimulated transcriptional activation of the PRL promoter in GH3 cells. TERP-1 and ERbeta protein levels were low to undetectable in cell lines, but E stimulated TERP-1. Because E treatment decreases ERbeta mRNA and ERalpha protein and increases levels of TERP-1 (which can suppress ERalpha/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.
Schreihofer
D A
DA
Department of Internal Medicine, University of Virginia, Charlottesville 22908, USA.
Stoler
M H
MH
Shupnik
M A
MA
D000818:Animals; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol