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Endocrinology Vol. 140, No. 6 2651-2658
Copyright © 1999 by The Endocrine Society

ARTICLES

Differential Regulation and Action of Estrogen Receptors {alpha} and ß in GH3 Cells1

Natasha A. Mitchner, Claire Garlick, Rosemary W. Steinmetz2 and Nira Ben-Jonathan

Department of Cell Biology, University of Cincinnati Medical School, Cincinnati, Ohio 45267

Address all correspondence and request for reprints to: Dr. Nira Ben-Jonathan, Department of Cell Biology, University of Cincinnati Medical School, 231 Bethesda Avenue, Cincinnati, Ohio 45267-0521. E-mail: nira.ben-jonathan{at}uc.edu

The pituitary lactotroph, a well established target for estrogens, expresses estrogen receptor-{alpha} (ER{alpha}) and -ß (ERß). A truncated isoform of ER{alpha}, named TERP, is expressed in the pituitary, but not in the uterus. In this study we used the somatolactotroph cell line, GH3 cells, to examine 1) the expression of ER{alpha}, TERP, or ERß and their regulation by estradiol; 2) the presence of receptor proteins; and 3) the effects of overexpressing ERß or TERP on estrogen induction of the PRL gene and activation of the estrogen response element (ERE).

Incubation of GH3 cells with estradiol (0.1–10 nM) produced dose-dependent increases in messenger RNA levels of ERß and TERP, but not ER{alpha}, as determined by quantitative RT-PCR. Cell incubation with 1 nM estradiol resulted in a time-dependent biphasic increase in TERP and a delayed rise in ERß, suggesting activation by both direct and indirect mechanisms. A polyclonal ERß antibody directed against an N-terminal synthetic peptide was generated. This antibody detected ERß-positive cells in ovarian granulosa cells and in many cells throughout the pituitary; its specificity was demonstrated by preabsorption with the synthetic peptide. The antibody detected a 58- to 60-kDa protein by Western blotting of ovarian, pituitary, and GH3 cell extracts. Cotransfection of ERß and reporter genes (PRL promoter/luciferase or ERE/luciferase) into GH3 cells resulted in a dose-dependent increase in estrogen-induced PRL gene expression, with a lesser activation of the ERE. A 20-kDa TERP protein was undetectable in untreated GH3 cells and was weakly induced by estradiol. Overexpression of TERP had no effect on estrogen induction of either PRL or ERE.

We conclude that 1) both ERß and TERP messenger RNAs in GH3 cells are increased by estradiol in a dose- and time-dependent manner, whereas ER{alpha} is not altered; 2) a 58-kDa ERß protein is expressed in both the pituitary and GH3 cells; and 3) overexpression of ERß increases estrogen-induced PRL gene expression.




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