Modulation of the levels of transforming growth factor beta messenger ribonucleic acids in human endometrial stromal...

We speculate that transforming growth factor beta (TGF beta) is involved in the predecidualization of human endometrial stromal cells (the progenitors of the decidual cells) during the late secretory phase of nonfertile, ovulatory cycles and in the completion of decidualization during fertile cycles after blastocyst implantation. In this study, the regulation of the levels of TGF beta mRNA levels in human endometrial stromal cells in culture was evaluated. TGF beta 1 and TGF beta 3 mRNAs were demonstrable by Northern analysis of total RNA from endometrial stromal cells maintained in serum-containing culture medium. TGF beta 2 mRNA was not detected by similar analyses of total RNA. The levels of TGF beta 3 mRNA in endometrial stromal cells increased in a time-dependent fashion after these cells were changed to serum-free medium. Platelet-derived growth factor acted, in a dose-dependent manner, to increase the levels of both TGF beta 1 and TGF beta 3 mRNAs in these cells. TGF beta 1 treatment caused an increase in the levels of TGF beta 1 mRNA and a decrease in the level of TGF beta 3 mRNA. The effects of platelet-derived growth factor and TGF beta 1 to increase the levels of TGF beta 1 mRNA were at least additive. Treatment of endometrial stromal cells with estradiol-17 beta caused an increase in the levels of TGF beta 1 and TGF beta 3 mRNAs. Treatment of stromal cells with medroxyprogesterone acetate (MPA, a synthetic progestin) also effected a small increase in the level of TGF beta 1 mRNA. The level of TGF beta 3 mRNA in endometrial stromal cells, however, was decreased by MPA treatment. The level of TGF beta 3 mRNA was greater in proliferative phase endometrial tissue than in secretory phase tissue. The levels of TGF beta 3 mRNA in decidua of the first trimester of pregnancy, in atrophic endometrium (from women treated with a GnRH agonist), and in endometrium from women ingesting oral progestin (MPA), were approximately one-fourth that in proliferative phase endometrium. These findings support the potential for modulation of TGF beta 1 and TGF beta 3 gene expression in endometrial stromal cells.