Possible role of transforming growth factor-β as a mediator of luteotropic action of prolactin in rat luteal cell cultures

PRL is known to be a hormone carrying luteotropic action in rats and enhances progesterone secretion by suppressing 20α-hydroxysteroid dehydrogenase (20αHSD) activity in the corpus luteum. In this study, we investigated the effects of PRL and transforming growth factor-β (TGFβ) on the 20αHSD activity of rat luteal cells in vitro and examined whether TGFβ is involved in the luteotropic action of PRL. 20αHSD activity of luteal cells (from midpseudopregnant rats), which had been suppressed by PRL in vivo, increased when the cells were cultured for 48 h without PRL addition. TGFβ (0.01, 0.1, 1.0, and 10.0 ng/ml) as well as PRL (2, 20, 200, and 2000 ng/ml) suppressed this increase in a dose-dependent manner. Furthermore, the suppressive effect of PRL on 20αHSD activity was significantly attenuated by anti-TGFβ antibody. Activin, having homology with TGFβ in its chemical structure, also suppressed the increase in enzyme activity, although the effect was much less marked than that of TGFβ. TGFβ or PRL did not affect total progestin (progesterone plus 20α-dihydroprogesterone) secretion, but induced reduction in 20α-dihydroprogesterone secretion during a 48-h culture period, without any alteration of DNA or protein content per culture dish. These results indicate that TGFβ, like PRL, can suppress luteal 20αHSD activity without producing nonspecific cell damage, and that the luteotropic action of PRL is at least in part mediated by TGFβ or an immunoreactive TGFβ-like substance(s).