T. Maruyama et al., Induction of thioredoxin, a redox-active protein, by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro, ENDOCRINOL, 140(1), 1999, pp. 365-372
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.