A technique to culture rabbit epithelial endometrial cells in chemically defined medium has been developed. Estrogens were found to promote cell division, whereas progesterone had an opposite effect. These cultured cells were found to be either noncycling (GO) or cycling. Both cell subpopulations were isolated, and it was found that the GO cells were the target of estrogens. Interaction between progesterone and the cycling cells was necessary to obtain an antagonistic effect on the estrogen action on the GO cells due to the production of a diffusible factor. A similar factor, probably a protein, appears to be produced by high density cultures that do not respond to estrogen stimulation. In the process of isolating this estrogen inhibitor factor, another one having estrogen-amplification effects was detected. It was also found that the cultured cells synthesize a glycoprotein called uteroglobin. Its production is regulated by estrogens and progesterone. Estradiol and progesterone decrease the number of estrogen receptors in cultures, apparently by different mechanisms of action. Cultured cells grown on floating collagen gels exhibit cycling growth kinetics. These cycles of cell proliferation and death are elicited by two diffusible factors made by the cells. These two factors inducing either cell death or cell proliferation, are apparently proteins. We will continue to study our experimental system by analyzing the mechanism of action of ovarian sex hormones in regulating cell proliferation, cell death, uteroglobin production, and hormone receptors, as well as isolating the factors regulating cell growth and estrogen effects. The endpoint of our research is to improve our comprehension of the mechanism by which sex hormones regulate proliferation and differentiation of endometrium. It is expected that the study of our hormone-responsive system will help to advance the understanding of the etiology and pathogenesis of endometrial hyperplasia and carcinoma in particular and hormone-related cancer in general. (D)
