Regulation of inhibin secretion in human placental cell culture by epidermal growth factor, transforming growth factors, and activin.

Abstract

In this study, the effects of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), TGF beta 1, and activin-A on inhibin secretion were investigated in primary culture of human placental cells. Immunoreactive inhibin in the culture medium was measured by immunoenzymatic assay. EGF stimulated testosterone-induced inhibin secretion in placental cells. Although testosterone alone induced only a slight enhancement of inhibin release in the culture, treatment of trophoblast cells with EGF and testosterone caused a significant increase in inhibin secretion, with immunoreactive inhibin levels much higher than those of testosterone or EGF alone. TGF alpha combined with human placental lactogen (hPL) had a stimulatory effect on inhibin secretion in placental cell culture. Simple addition of either TGF alpha or hPL to the culture did not show any effect on inhibin secretion in placental cells. A remarkable augmentation of inhibin secretion was obtained after the trophoblasts were exposed to both TGF alpha and hPL simultaneously. TGF beta 1 and activin-A showed synergistic effects to suppress inhibin secretion in placental cells. TGF beta 1 alone did not show any action on inhibin secretion, and activin-A alone induced a small decrease in inhibin release in the culture. In the presence of activin-A, addition of TGF beta 1 to the culture induced a profound decrease in immunoreactive inhibin levels in the medium. Activin-A could also suppress hCG-induced inhibin secretion in placental cells. Addition of hCG alone resulted in a small, but not significant, increase in inhibin release in the cultured cells, whereas the presence of activin-A combined with hCG in the culture conversely decreased inhibin secretion in the culture, with immunoreactive inhibin levels significantly lower than those in the presence of hCG or activin-A alone. These findings suggest that EGF and TGF alpha, alone or in combination with other hormones, may be stimulators, and TGF beta and activin may act as suppressors of inhibin secretion in human placental cells.