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Endocrinology Vol. 139, No. 11 4708-4713
Copyright © 1998 by The Endocrine Society

ARTICLES

Stromal Progesterone Receptors Mediate the Inhibitory Effects of Progesterone on Estrogen-Induced Uterine Epithelial Cell Deoxyribonucleic Acid Synthesis1

Takeshi Kurita, Peter Young, Joel R. Brody, John P. Lydon, Bert W. O’Malley and Gerald R. Cunha

Department of Anatomy (T.K., P.Y., J.R.B., G.R.C.), University of California, San Francisco, California 94143; Department of Cell Biology (J.P.L., B.W.O.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Dr. Gerald R. Cunha, Cancer Research Building, UCSF Mt. Zion Cancer Center, University of California, San Francisco, California. E-mail: gcunha{at}itsa.ucsf

The role of epithelial and stromal progesterone (P) receptors (PR) in the regulation of uterine epithelial DNA synthesis by P was investigated by analyzing the four types of tissue recombinants prepared with uterine stroma (S) and epithelium (E) from wild-type (wt) and PR knockout (PRKO) mice: wt-S + wt-E, PRKO-S + PRKO-E, wt-S + PRKO-E, and PRKO-S + wt-E. 17-ß estradiol (E2) stimulated DNA synthesis in all four types of tissue recombinants. On the other hand, P inhibited E2-induced DNA synthesis only in tissue recombinants prepared with wild-type (PR-positive) stroma (wt-S + wt-E or wt-S + PRKO-E) but not knockout (PR-negative) stroma (PRKO-S + wt-E or PRKO-S + PRKO-E). These results clearly demonstrate that the inhibitory effect of P on uterine epithelial DNA synthesis is mediated by stromal PR. Epithelial PR is neither necessary nor sufficient for P inhibition of E2-induced epithelial DNA synthesis.




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