C. Brand et al., Smad3 is involved in the intracellular signaling pathways that mediate theinhibitory effects of transforming growth factor-beta on StAR expression, BIOC BIOP R, 253(3), 1998, pp. 780-785
Citations number
24
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Transforming growth factor beta s (TGF beta s) constitute a family of dimer
ic proteins that regulate growth and differentiation of many cell types. TG
F beta 1 is also a potent autocrine regulator of adrenocortical steroidogen
esis. We have recently shown that in primary cultures of bovine fasciculo-r
eticularis cells, the main target of TGF beta is the steroidogenic acute re
lay protein (StAR), a key protein necessary for intramitochondrial choleste
rol transport, Here, we show that StAR expression is also inhibited by TGF
beta 1 in the human adrenocortical carcinoma cell line NCI-H295R. This inhi
bitory effect is mediated by Smad proteins. Indeed, we found that overexpre
ssion of wild-type Smad3 inhibited endogenous StAR mRNA expression while ov
erexpression of a dominant negative Smad3 protein reversed the inhibitory e
ffect of TGF beta 1 on StAR mRNA expression. Taken together, these results
demonstrate that the Smad3 protein is involved in TGF beta-dependent regula
tion of steroidogenesis. (C) 1998 Academic Press.