Effect of transforming growth factor-beta 1 on the insulin-like growth factor system in cultured porcine Leydig cells.

Using as a model system, primary cultures of porcine Leydig cells, we have shown that transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml, 72 h) antagonizes the stimulatory action of insulin-like growth factor-I (IGF-I) on luteinizing hormone (LH/hCG) receptors. We therefore investigated the action of TGF-beta 1 on the different components of the IGF system, namely, IGF-I, II, IGF binding proteins (IGFBPs) and IGF-I receptor present in testicular Leydig cells. TGF-beta 1 was shown to decrease in a dose and time dependent manner the binding of 125I-IGF-I to Leydig cells. The maximal (40% decrease) effect was obtained with 1.3 ng/ml (0.05 nM) after 72 h of treatment. Such a decrease in IGF-I binding by TGF-beta 1 treatment was shown to be related to the number of receptor but not to their affinity. Affinity labeling of these receptors by covalently binding them to 125I-IGF-I with disuccinimidyl suberate and subsequent electrophoretic analysis of the labeled complex revealed that the inhibitory action of TGF-beta 1 (2 ng/ml, 72 h) occurs at the level of a 135 kDa protein which represents the classical form of the binding subunit of the IGF-I receptor. Moreover, our study indicates that TGF-beta 1 was unable to affect the other components of the IGF system in cultured porcine Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)