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Biochem Biophys Res Commun. 1998 Dec 30;253(3):780-5.

Smad3 is involved in the intracellular signaling pathways that mediate the inhibitory effects of transforming growth factor-beta on StAR expression.

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INSERM Unité 244, Commissariat à l'Energie Atomique, Départment de Biologie Moléculaire et Structurale, Grenoble, France.


Transforming growth factor betas (TGFbetas) constitute a family of dimeric proteins that regulate growth and differentiation of many cell types. TGFbeta1 is also a potent autocrine regulator of adrenocortical steroidogenesis. We have recently shown that in primary cultures of bovine fasciculo-reticularis cells, the main target of TGFbeta is the steroidogenic acute relay protein (StAR), a key protein necessary for intramitochondrial cholesterol transport. Here, we show that StAR expression is also inhibited by TGFbeta1 in the human adrenocortical carcinoma cell line NCI-H295R. This inhibitory effect is mediated by Smad proteins. Indeed, we found that overexpression of wild-type Smad3 inhibited endogenous StAR mRNA expression while overexpression of a dominant negative Smad3 protein reversed the inhibitory effect of TGFbeta1 on StAR mRNA expression. Taken together, these results demonstrate that the Smad3 protein is involved in TGFbeta-dependent regulation of steroidogenesis.

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