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Transforming Growth Factor β 1 Decreases Cholesterol Supply to Mitochondria via Repression of Steroidogenic Acute Regulatory Protein Expression

Abstract : Transforming growth factor-betas (TGF-betas) constitute a family of dimeric proteins that affect growth and differentiation of many cell types. TGF-beta1 has also been proposed to be an autocrine regulator of adrenocortical steroidogenesis, acting mainly by decreasing the expression of cytochrome P450c17. Here, we demonstrate that TGF-beta1 has a second target in bovine adrenocortical cells, namely the steroidogenic acute regulatory protein (StAR). Indeed, supplying cells with steroid precursors revealed that TGF-beta1 inhibited two steps in the steroid synthesis pathway, one prior to pregnenolone production and another corresponding to P450c17. More specifically, TGF-beta1 inhibited pregnenolone production but neither the conversion of 25-hydroxycholesterol to pregnenolone nor P450scc activity. Thus, TGF-beta1 must decrease the cholesterol supply to P450scc. We therefore examined the effect of TGF-beta1 on the expression of StAR, a mitochondrial protein implicated in intramitochondrial cholesterol transport. TGF-beta1 decreased the steady state level of StAR mRNA in a time- and concentration-dependent manner. This inhibition occurs at the level of StAR transcription and depends on RNA and protein synthesis. It is likely that the TGF-beta1-induced decrease of StAR expression that we report here may be expanded to other steroidogenic cells in which a decrease of cholesterol accessibility to P450scc by TGF-beta1 has been hypothesized.
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https://hal.univ-grenoble-alpes.fr/hal-02459001
Contributeur : Nadia Cherradi <>
Soumis le : mercredi 29 janvier 2020 - 10:00:17
Dernière modification le : lundi 20 juillet 2020 - 10:16:02

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Céline Brand, Nadia Cherradi, Geneviève Defaye, Anna Chinn, Edmond Chambaz, et al.. Transforming Growth Factor β 1 Decreases Cholesterol Supply to Mitochondria via Repression of Steroidogenic Acute Regulatory Protein Expression. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1998, 273 (11), pp.6410-6416. ⟨10.1074/jbc.273.11.6410⟩. ⟨hal-02459001⟩

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