Stromal progesterone receptors mediate the inhibitory effects of progesterone on estrogen-induced uterine epithelial cell deoxyribonucleic acid synthesis.
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-Beta 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.
Kurita
T
T
Department of Anatomy, University of California, San Francisco 94143, USA.
Young
P
P
Brody
J R
JR
Lydon
J P
JP
O'Malley
B W
BW
Cunha
G R
GR
D000818:Animals; D001345:Autoradiography; D004247:DNA / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D011995:Recombination, Genetic; D017154:Stromal Cells / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D004967:Estrogens; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D004247:DNA