Stimulation of progesterone receptors by phorbol ester and cyclic AMP in fetal uterine cells in culture.
The role of growth factor signal transducers in the induction of the progesterone receptor by epidermal growth factor (EGF) and the potential sites of EGF antagonism by an antiestrogen were studied in fetal uterine cells in culture. The effects of EGF and estradiol were not additive, suggesting that EGF and estradiol are acting through common mechanisms where antiestrogens could possibly intervene. Fetal uterine cells in culture were found to contain specific, high affinity binding sites for [125I]EGF. Estradiol treatment of the cells led to a higher number of binding sites, but the site of action of 4-hydroxytamoxifen is not the EGF receptor because this antiestrogen had no effect on EGF binding. Activation of protein kinase C by a phorbol ester (12-O-tetradecanoylphorbol 13-acetate) increased progesterone receptor levels to a similar extent as EGF or estradiol. Increasing the intracellular cAMP concentrations by either adding dibutyryl cyclic AMP or activating adenylate cyclase with forskolin also raised progesterone receptor concentrations. Neither the phorbol ester nor dibutyryl cAMP had any effect on cell proliferation. 4-Hydroxytamoxifen completely abolished the effects of the phorbol ester and cAMP. In conclusion, the levels of an estrogen-induced steroid hormone receptor can be regulated by molecules involved in the signal transduction pathway of peptide factors. Moreover, in fetal uterine cells, a potent antiestrogen appears to act as a multiple antagonist but only on an estrogen-inducible response.
Sumida
C
C
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
Pasqualini
J R
JR
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D011493:Protein Kinase C / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism
D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D005576:Colforsin; D004958:Estradiol; D004815:Epidermal Growth Factor; D003994:Bucladesine; D000242:Cyclic AMP; D066246:ErbB Receptors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate