Transforming Growth Factor β 1 Decreases Cholesterol Supply to Mitochondria via Repression of Steroidogenic Acute Regulatory Protein Expression
Céline Brand
(1)
,
Nadia Cherradi
(2)
,
Geneviève Defaye
(3)
,
Anna Chinn
,
Edmond Chambaz
,
Jean-Jacques Feige
(4)
,
Sabine Bailly
(5)
1
Département de Biologie Moléculaire et Structurale, Biochìmìe des Régulations Cellulaires Endocrines, INSERM Unité 244
2 Department of Internal Medicine, Faculty of Medicine, University Hospital of Geneva
3 Angiogenèse hormono-régulée et angiogenèse tumorale
4 LAPV - Angiogenèse hormono-regulée et angiogenèse tumorale
5 BAL - Famille BMP dans l'angiogenèse et la lymphangiogenèse
2 Department of Internal Medicine, Faculty of Medicine, University Hospital of Geneva
3 Angiogenèse hormono-régulée et angiogenèse tumorale
4 LAPV - Angiogenèse hormono-regulée et angiogenèse tumorale
5 BAL - Famille BMP dans l'angiogenèse et la lymphangiogenèse
Céline Brand
- Fonction : Auteur
- PersonId : 833879
Nadia Cherradi
- Fonction : Auteur
- PersonId : 180012
- IdHAL : nadia-cherradi
- ORCID : 0000-0002-4292-774X
- IdRef : 185869831
Anna Chinn
- Fonction : Auteur
Edmond Chambaz
- Fonction : Auteur
Sabine Bailly
- Fonction : Auteur
- PersonId : 759262
- ORCID : 0000-0003-1043-7030
- IdRef : 078713293
Résumé
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.
Domaines
Sciences de l'Homme et SociétéFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Transforming Growth Factor β 1 Decreases Cholesterol Supply to Mitochondria via Repression of Steroidogenic Acute Regulatory Protein Expression
|
Résumé |
en
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.
|
Auteur(s) |
Céline Brand
1
, Nadia Cherradi
2
, Geneviève Defaye
3
, Anna Chinn
, Edmond Chambaz
, Jean-Jacques Feige
4
, Sabine Bailly
5
1
Département de Biologie Moléculaire et Structurale, Biochìmìe des Régulations Cellulaires Endocrines, INSERM Unité 244
( 580162 )
- 17 rue des Martyrs
CEA Grenoble
F-38054 Grenoble
- France
2
Department of Internal Medicine, Faculty of Medicine, University Hospital of Geneva
( 580163 )
- CH-1211 Geneva 14
- Suisse
3
Angiogenèse hormono-régulée et angiogenèse tumorale
( 2651 )
- Cea 17, Rue Des Martyrs 38054 GRENOBLE CEDEX 9
- France
4
LAPV -
Angiogenèse hormono-regulée et angiogenèse tumorale
( 40553 )
- France
5
BAL -
Famille BMP dans l'angiogenèse et la lymphangiogenèse
( 552921 )
- 17 avenue des Martyrs 38 054 Grenoble cedex 9
- France
|
Date de publication |
1998-03-13
|
Volume |
273
|
Numéro |
11
|
Page/Identifiant |
6410-6416
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Domaine(s) |
|
DOI | 10.1074/jbc.273.11.6410 |
Pubmed Id | 9497372 |
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