Limits...
SF-1 a key player in the development and differentiation of steroidogenic tissues.

Val P, Lefrançois-Martinez AM, Veyssière G, Martinez A - Nucl. Recept. (2003)

Bottom Line: SF-1 is also an essential regulator of genes involved in the sex determination cascade.In particular, the role of SF-1 in the hormonal responsiveness of steroidogenic genes promoters is still a subject of debate.It also summarizes the pros and cons regarding the presumed role of SF-1 in cAMP signalling.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMR CNRS 6547, Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Clermont II, Complexe Universitaire des Cézeaux, 24 avenue des Landais, 63177 Aubiere Cedex, France. a-marie.lefrancois-martinez@univ-bpclermont.fr

ABSTRACT
Since its discovery in the early 1990s, the orphan nuclear receptor SF-1 has been attributed a central role in the development and differentiation of steroidogenic tissues. SF-1 controls the expression of all the steroidogenic enzymes and cholesterol transporters required for steroidogenesis as well as the expression of steroidogenesis-stimulating hormones and their cognate receptors. SF-1 is also an essential regulator of genes involved in the sex determination cascade. The study of SF-1 mice and of human mutants has been of great value to demonstrate the essential role of this factor in vivo, although the complete adrenal and gonadal agenesis in knock-out animals has impeded studies of its function as a transcriptional regulator. In particular, the role of SF-1 in the hormonal responsiveness of steroidogenic genes promoters is still a subject of debate. This extensive review takes into account recent data obtained from SF-1 haploinsufficient mice, pituitary-specific knock-outs and from transgenic mice experiments carried out with SF-1 target gene promoters. It also summarizes the pros and cons regarding the presumed role of SF-1 in cAMP signalling.

No MeSH data available.


Related in: MedlinePlus

MIS promoter. Binding sites for the transcription factors required for proper MIS expression are shown. Their position in human MIS promoter is indicated (hMIS). WT1 and Dax-1 are able to respectively stimulate or repress MIS promoter activity by interacting with SF-1 bound to its proximal responsive element. Effect of the mutation of the proximal SFRE or SOX9 responsive element introduced by knock-in in mice on Müllerian ducts regression is indicated. Abreviations : Sox BS, SOX factors binding site; SFRE, SF-1 responsive element.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC240021&req=5

Figure 3: MIS promoter. Binding sites for the transcription factors required for proper MIS expression are shown. Their position in human MIS promoter is indicated (hMIS). WT1 and Dax-1 are able to respectively stimulate or repress MIS promoter activity by interacting with SF-1 bound to its proximal responsive element. Effect of the mutation of the proximal SFRE or SOX9 responsive element introduced by knock-in in mice on Müllerian ducts regression is indicated. Abreviations : Sox BS, SOX factors binding site; SFRE, SF-1 responsive element.

Mentions: SF-1 and MIS are coexpressed in developing Sertoli cells [104], and SF-1, in association with SOX9 [105], GATA-4 [106] and WT-1 [107] is able to stimulate MIS promoter activity in transient transfections (figure 3). Male SF-1 mice show Müllerian duct persistence [29,34,50]. However, the absence of gonads in these animals does not allow a conclusion on a direct effect of SF-1 to be drawn. This difficulty was overcome by mutating the proximal SF-1 responsive element of the MIS promoter by homologous recombination with the endogenous MIS locus. This mutation reduces MIS accumulation albeit to an extent which is insufficient to prevent Müllerian duct regression, whereas when the SOX9 binding site is mutated by the same procedure, there is Müllerian duct persistence in male mice (figure 3). These results suggest that SOX9 triggers MIS expression whereas SF-1 acts as a quantitative regulator [108].


SF-1 a key player in the development and differentiation of steroidogenic tissues.

Val P, Lefrançois-Martinez AM, Veyssière G, Martinez A - Nucl. Recept. (2003)

MIS promoter. Binding sites for the transcription factors required for proper MIS expression are shown. Their position in human MIS promoter is indicated (hMIS). WT1 and Dax-1 are able to respectively stimulate or repress MIS promoter activity by interacting with SF-1 bound to its proximal responsive element. Effect of the mutation of the proximal SFRE or SOX9 responsive element introduced by knock-in in mice on Müllerian ducts regression is indicated. Abreviations : Sox BS, SOX factors binding site; SFRE, SF-1 responsive element.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC240021&req=5

Figure 3: MIS promoter. Binding sites for the transcription factors required for proper MIS expression are shown. Their position in human MIS promoter is indicated (hMIS). WT1 and Dax-1 are able to respectively stimulate or repress MIS promoter activity by interacting with SF-1 bound to its proximal responsive element. Effect of the mutation of the proximal SFRE or SOX9 responsive element introduced by knock-in in mice on Müllerian ducts regression is indicated. Abreviations : Sox BS, SOX factors binding site; SFRE, SF-1 responsive element.
Mentions: SF-1 and MIS are coexpressed in developing Sertoli cells [104], and SF-1, in association with SOX9 [105], GATA-4 [106] and WT-1 [107] is able to stimulate MIS promoter activity in transient transfections (figure 3). Male SF-1 mice show Müllerian duct persistence [29,34,50]. However, the absence of gonads in these animals does not allow a conclusion on a direct effect of SF-1 to be drawn. This difficulty was overcome by mutating the proximal SF-1 responsive element of the MIS promoter by homologous recombination with the endogenous MIS locus. This mutation reduces MIS accumulation albeit to an extent which is insufficient to prevent Müllerian duct regression, whereas when the SOX9 binding site is mutated by the same procedure, there is Müllerian duct persistence in male mice (figure 3). These results suggest that SOX9 triggers MIS expression whereas SF-1 acts as a quantitative regulator [108].

Bottom Line: SF-1 is also an essential regulator of genes involved in the sex determination cascade.In particular, the role of SF-1 in the hormonal responsiveness of steroidogenic genes promoters is still a subject of debate.It also summarizes the pros and cons regarding the presumed role of SF-1 in cAMP signalling.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMR CNRS 6547, Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Clermont II, Complexe Universitaire des Cézeaux, 24 avenue des Landais, 63177 Aubiere Cedex, France. a-marie.lefrancois-martinez@univ-bpclermont.fr

ABSTRACT
Since its discovery in the early 1990s, the orphan nuclear receptor SF-1 has been attributed a central role in the development and differentiation of steroidogenic tissues. SF-1 controls the expression of all the steroidogenic enzymes and cholesterol transporters required for steroidogenesis as well as the expression of steroidogenesis-stimulating hormones and their cognate receptors. SF-1 is also an essential regulator of genes involved in the sex determination cascade. The study of SF-1 mice and of human mutants has been of great value to demonstrate the essential role of this factor in vivo, although the complete adrenal and gonadal agenesis in knock-out animals has impeded studies of its function as a transcriptional regulator. In particular, the role of SF-1 in the hormonal responsiveness of steroidogenic genes promoters is still a subject of debate. This extensive review takes into account recent data obtained from SF-1 haploinsufficient mice, pituitary-specific knock-outs and from transgenic mice experiments carried out with SF-1 target gene promoters. It also summarizes the pros and cons regarding the presumed role of SF-1 in cAMP signalling.

No MeSH data available.


Related in: MedlinePlus