Induction of thioredoxin, a redox-active protein, by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro

Human thioredoxin (hTrx) is a cellular redox-active protein that catalyzes dithiol/disulfide exchange reactions, thus controlling multiple biological functions, including cell growth-promoting activity. Here we show that the expression of hTrx protein and messenger RNA was up-regulated by incubation with 17 beta-estradiol (E-2) in primary culture of stromal cells isolated from human endometrium. Maximal enhancement of hTrx protein and messenger R NA was observed after 6-12 h of incubation with 10-100 nM E-2, and the enha ncing effect was suppressed by tamoxifen, an estrogen antagonist. Release o f hTrx into the culture medium was markedly augmented after 5-day exposure of E-2 plus progesterone (P) accompanied by in vitro differentiation of end ometrial stromal cells (decidualization). Immunocytochemical studies showed that hTrx was localized in the nucleus, nucleolus, and cytosol in the stro mal cells. Strongly enhanced immunoreactivity for hTrx was observed in the E-2-treated cells, whereas there was no apparent difference in the pattern of subcellular localization among the untreated and E-2- and/or P-treated c ells. Although 1-50 mu g/ml recombinant hTrx alone did not promote endometr ial stromal cell growth, epidermal growth factor-dependent mitogenesis was additively enhanced by hTrx. Our results indicate that hTrx modulates endom etrial cell growth, acting as a comitogenic factor for epidermal growth fac tor, which is known to be a mediator of estrogen action. It is also suggest ed that hTrx is deeply involved in the hormonal control of the endometrium by E-2 and P, playing a regulatory role in endometrial cell growth and diff erentiation.