The mechanism of signal transduction by transforming growth factor-beta 1 (TGF-beta 1) is largely unknown. In this study, TGF-beta 1 was able to stimulate 45Ca2+ uptake in cultured rat Sertoli cells. In contrast to the rapid stimulation of 45Ca2+ uptake previously observed in response to FSH (< 1 min), the response to TGF-beta 1 required several hours and was abolished by actinomycin-D. Although TGF-beta 1 had no effect on basal calcium uptake before 1 h, it completely inhibited the FSH-stimulated calcium uptake in short term incubations (2 and 20 min). These effects of TGF-beta 1 on calcium metabolism may be directly related to the ability of this cytokine to regulate cell growth and differentiation in many cell systems.