Estrogen Induction of Progesterone Receptor and Its Relationship to Cell Multiplication Rate in the Rat Pituitary Tumor Cell Line C29RAP

Abstract

The purpose of the present experiments is to compare the estrogen induction of a specific protein, cytoplasmic progesterone receptor (PR), and estrogen-stimulated cell multiplication in the C₂9RAP rat pituitary tumor cell line in animals and in cell culture. In tumors established by the injection of cells into isogenic rats, PR was reduced by 50% in ovariectomized rats compared to intact females carrying the same tumor cells. Estrogen replacement with 17β-estradiol (E₂) Silastic implants in ovariectomized rats increased the PR concentration in the tumor cells 4–5 times above the control values in ovariectomized rats without E₂ replacement. In cell cultures, PR was increased 3-to 4-fold after exposure to E₂ (0.03–30 nM) for 48 h. The PR concentration was increased specifically by estrone, E₂, and estriol but not by testosterone or dihydrotestosterone. The induction of PR was dose related; maximal induction was obtained at an E₂ concentration of 3 nM. A latent period of more than 6 h for the induction of PR by E₂ was observed; maximal induction was obtained within 48 h. The cell multiplication rate of C₂9RAP cells injected into intact rats has previously been shown to be increased by E₂ administration. However, in the present experiments, the cell multiplication rate of these cells in culture for up to 9 days was not influenced by E₂ at concentrations between 0.03–30 nM. It is concluded that while C₂9RAP tumor cells are responsive to E₂ both in animals and in cell culture in terms of the induction of PR, these cells are responsive to E₂ administration in terms of cell multiplication in animals but not in cell culture under the conditions employed. These results are consistent with the hypothesis that E₂ may stimulate tumor growth in animals indirectly by suppression of an inhibitory factor(s).