Inhibition by 12-O-tetradecanoylphorbol-13-acetate of 17 beta-estradiol-induced initiation of DNA synthesis in rabbit endometrial cells in culture.
The initial effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 17 beta-estradiol on initiation of DNA synthesis by primary cultures of estrogen-responsive rabbit uterine epithelial cells were determined by autoradiography after a [3H]thymidine pulse. In contrast to the stimulatory response produced by estradiol, TPA (1.6 x 10(-7) M) reduced the fraction of cells synthesizing DNA for up to 48 h. Cells synthesizing DNA at the time TPA was added were found to be less sensitive to its inhibitory effect, suggesting that TPA blocked the cells from entering the S phase of the cell cycle. The cells were unresponsive to estradiol during the TPA-induced inhibitory period, although TPA did not interfere with the binding of [3H]estradiol to the hormonal whole-cell receptors. The results indicted that TPA acted to reduce the fraction of cells initiating DNa synthesis by a mechanism that appears to be independent of estrogen involvement.
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D010704:Phorbols / Q000633:toxicity*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D010704:Phorbols; D004958:Estradiol; D004247:DNA; D013755:Tetradecanoylphorbol Acetate