Control of Progesterone Receptors in Fetal Uterine Cells in Culture: Effects of Estradiol, Progestins, Antiestrogens, and Growth Factors*

Abstract

Cells from the fetal uterus of the guinea pig have been grown as monolayer cell cultures both as primary cultures and through several passages. The cells have a fibroblast-like morphology and ultrastructure, and the subcultures are estrogen responsive. Estradiol induced a 2- to 3-fold increase in specific binding of [3H]R5020 by 9 days in culture, with no effect on proliferation. This binding has the characteristics of the progesterone receptor from the fetal guinea pig uterus (saturable, high affinity, specific for progestins). The increase in progesterone receptor depended on the dose of estradiol, with a half-maximal response at about 5 X 10(-11) M. Progesterone receptor concentrations were inhibited to below basal levels by progesterone and R5020 and the nonsteroidal antiestrogens, tamoxifen, and 4-hydroxytamoxifen. Both progestins and antiestrogens antagonized the stimulatory effect of estradiol. None of these compounds had any effect on cell growth. On the other hand, insulin and epidermal growth factor caused a great increase in cell proliferation. Insulin alone had no effect on progesterone receptor concentrations, but epidermal growth factor stimulated the progesterone receptor about as much as estradiol. Furthermore, coincubation of insulin with estradiol produced a synergistic effect. Estrogen receptor levels were low or undetectable at any time in either the primary culture or the subcultures. It is concluded that fetal uterine cells in culture can serve as a good in vitro model for study of the control of the progesterone receptor in a fetal target tissue.