Tissue Compartment-Specific Estrogen Receptor-α Participation in the Mouse Uterine Epithelial Secretory Response**Presented in part at the 30th Annual Meeting of the Society for the Study of Reproduction, Portland, Oregon, August 1997. This work was supported by NIH Grants AG-15500 (to P.S.C.), ES-08272 (to D.B.L.), and CA-05388 and AG-13784 (to G.R.C.).

Abstract

17␤-Estradiol (E 2 ) acts through the estrogen receptor (ER) to regulate uterine epithelial cell growth, proliferation, differentiation, and secretory protein production.We have previously shown that E 2induced uterine epithelial proliferation is mediated indirectly by ER␣-positive stroma; epithelial ER␣ is neither necessary nor sufficient for E 2 -induced uterine epithelial mitogenesis.In the present study, we addressed the question of whether production of uterine epithelial secretory proteins and their messenger RNAs (mRNAs) requires ER␣ in stroma, epithelium, or both by analyzing tissue recombinations composed of uterine tissue from adult ER␣ knockout (ko) and neonatal BALB/c (wt) mice.Stroma (S) and epithelium (E) were separated by trypsinization, and four types of uterine tissue recombinants were prepared: wt-S ϩ wt-E, wt-S ϩ ko-E, ko-S ϩ wt-E, and ko-S ϩ ko-E.These tissue recombinants were grown as subrenal capsule grafts in intact female nude mice for 4 weeks, at which time the hosts were ovariectomized.To assess the production of secretory proteins and their mRNAs, 1 week after ovariectomy the hosts were given three daily injections of oil or E 2 (100 ng), and then 24 h later the grafts were recovered and used for either ER or lactoferrin (LF) immunohistochemistry.To assess steady state mRNA levels by Northern blotting, hosts received one injection of oil or E 2 24 h before