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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

A model for LHβ promoter repression by a physical interaction between AR and SF-1. (After Jorgensen and Nilson, Ref. [201]) In the presence of elevated androgen concentrations, AR (androgen receptor) interacts with SF-1 on LHβ promoter, preventing interaction of Egr-1 with its response elements. LHβ is then turned off. A GnRH pulse (resulting from a reduction in circulating androgen concentrations), favours Egr-1 transcription, increasing its accumulation. In turn, Egr-1 displaces AR from SF-1 and favours an active setting of transcription factors on LHβ promoter. LHβ transcription is then triggered. The resulting LH protein production in turn stimulates androgens production by the gonads.
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Figure 6: A model for LHβ promoter repression by a physical interaction between AR and SF-1. (After Jorgensen and Nilson, Ref. [201]) In the presence of elevated androgen concentrations, AR (androgen receptor) interacts with SF-1 on LHβ promoter, preventing interaction of Egr-1 with its response elements. LHβ is then turned off. A GnRH pulse (resulting from a reduction in circulating androgen concentrations), favours Egr-1 transcription, increasing its accumulation. In turn, Egr-1 displaces AR from SF-1 and favours an active setting of transcription factors on LHβ promoter. LHβ transcription is then triggered. The resulting LH protein production in turn stimulates androgens production by the gonads.

Mentions: An unexpected repressor of SF-1 activity is the androgen receptor. The increase in plasmatic LH concentrations which is induced by GnRH leads to increased sex steroid production by the gonads. In turn, sex steroids exert a negative feedback on GnRH and LH synthesis (figure 6). Recently, Jorgensen and Nilson, have elegantly demonstrated that androgen receptor was able to repress LH-β promoter transactivation by interacting with SF-1 LBD [154]. Under low GnRH conditions, AR blocks the functional interaction between SF-1 and Ptx1/Egr-1. When GnRH concentrations in pituitary gonadotropes increase, Egr-1 expression is induced [156] and allows recruitment of Ptx-1 as well as AR displacement, resulting in the formation of an activating complex composed of SF-1, Egr-1 and Ptx1. When circulating androgens increase, activated AR displaces Egr-1 and Ptx1, thus repressing LH-β transcription in response to SF-1 [154]. This model (figure 6) perfectly illustrates the complex interactions that are required fo SF-1 target genes activation. It is likely that such mechanisms may participate to the control of SF-1 target genes expression in response to cAMP increases.


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)

A model for LHβ promoter repression by a physical interaction between AR and SF-1. (After Jorgensen and Nilson, Ref. [201]) In the presence of elevated androgen concentrations, AR (androgen receptor) interacts with SF-1 on LHβ promoter, preventing interaction of Egr-1 with its response elements. LHβ is then turned off. A GnRH pulse (resulting from a reduction in circulating androgen concentrations), favours Egr-1 transcription, increasing its accumulation. In turn, Egr-1 displaces AR from SF-1 and favours an active setting of transcription factors on LHβ promoter. LHβ transcription is then triggered. The resulting LH protein production in turn stimulates androgens production by the gonads.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: A model for LHβ promoter repression by a physical interaction between AR and SF-1. (After Jorgensen and Nilson, Ref. [201]) In the presence of elevated androgen concentrations, AR (androgen receptor) interacts with SF-1 on LHβ promoter, preventing interaction of Egr-1 with its response elements. LHβ is then turned off. A GnRH pulse (resulting from a reduction in circulating androgen concentrations), favours Egr-1 transcription, increasing its accumulation. In turn, Egr-1 displaces AR from SF-1 and favours an active setting of transcription factors on LHβ promoter. LHβ transcription is then triggered. The resulting LH protein production in turn stimulates androgens production by the gonads.
Mentions: An unexpected repressor of SF-1 activity is the androgen receptor. The increase in plasmatic LH concentrations which is induced by GnRH leads to increased sex steroid production by the gonads. In turn, sex steroids exert a negative feedback on GnRH and LH synthesis (figure 6). Recently, Jorgensen and Nilson, have elegantly demonstrated that androgen receptor was able to repress LH-β promoter transactivation by interacting with SF-1 LBD [154]. Under low GnRH conditions, AR blocks the functional interaction between SF-1 and Ptx1/Egr-1. When GnRH concentrations in pituitary gonadotropes increase, Egr-1 expression is induced [156] and allows recruitment of Ptx-1 as well as AR displacement, resulting in the formation of an activating complex composed of SF-1, Egr-1 and Ptx1. When circulating androgens increase, activated AR displaces Egr-1 and Ptx1, thus repressing LH-β transcription in response to SF-1 [154]. This model (figure 6) perfectly illustrates the complex interactions that are required fo SF-1 target genes activation. It is likely that such mechanisms may participate to the control of SF-1 target genes expression in response to cAMP increases.

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