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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

Adrenals and gonads development – SF-1 expression patterns. The key events of steroidogenic tissues development in mice are shown. Molecular players in male sex (SRY, SOX9, SF-1, Dax-1) and female sex determination (Wnt4, Dax-1) are shown. Dax-1 function in sex determination is still unclear. Abreviations : E, embryonic day; dpc, days post coïtum ; dpp, days post partum; dpo, days post ovulation. SF-1 levels of expression are schematically presented below the time scale.
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Figure 2: Adrenals and gonads development – SF-1 expression patterns. The key events of steroidogenic tissues development in mice are shown. Molecular players in male sex (SRY, SOX9, SF-1, Dax-1) and female sex determination (Wnt4, Dax-1) are shown. Dax-1 function in sex determination is still unclear. Abreviations : E, embryonic day; dpc, days post coïtum ; dpp, days post partum; dpo, days post ovulation. SF-1 levels of expression are schematically presented below the time scale.

Mentions: As expected from its function as an essential regulator of steroidogenesis, SF-1 is expressed in the testes and ovaries as early as their anlages appear (figure 2). In the ovary SF-1 expression rapidly decreases during development and increases after birth [26-28]. Though the placenta is a major steroid producing tissue during pregnancy, it only shows slight SF-1 expression, detected by RT-PCR [29], but not by in situ hybridisation [30] nor by northern-blot [31]. Moreover, SF-1 knock-out mice do not show placental development nor placental steroid synthesis defects [29]. Ben-Zimra et al. have confirmed that SF-1 is dispensable in the placenta by showing that AP2 can substitute for SF-1 to induce P450scc expression in this tissue [32]. SF-1 expression has also been detected in the pituitary anlage, in the precursors of gonadotrope cells that control reproductive function and in the ventro-medial hypothalamus (VMH) which regulates the gonadotrope axis as well as some aspects of metabolism [33-35]. At last, SF-1 has also been detected in skin [36] where it is associated to steroidogenic enzymes [37-39] and in the spleen [31,40].


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)

Adrenals and gonads development – SF-1 expression patterns. The key events of steroidogenic tissues development in mice are shown. Molecular players in male sex (SRY, SOX9, SF-1, Dax-1) and female sex determination (Wnt4, Dax-1) are shown. Dax-1 function in sex determination is still unclear. Abreviations : E, embryonic day; dpc, days post coïtum ; dpp, days post partum; dpo, days post ovulation. SF-1 levels of expression are schematically presented below the time scale.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Adrenals and gonads development – SF-1 expression patterns. The key events of steroidogenic tissues development in mice are shown. Molecular players in male sex (SRY, SOX9, SF-1, Dax-1) and female sex determination (Wnt4, Dax-1) are shown. Dax-1 function in sex determination is still unclear. Abreviations : E, embryonic day; dpc, days post coïtum ; dpp, days post partum; dpo, days post ovulation. SF-1 levels of expression are schematically presented below the time scale.
Mentions: As expected from its function as an essential regulator of steroidogenesis, SF-1 is expressed in the testes and ovaries as early as their anlages appear (figure 2). In the ovary SF-1 expression rapidly decreases during development and increases after birth [26-28]. Though the placenta is a major steroid producing tissue during pregnancy, it only shows slight SF-1 expression, detected by RT-PCR [29], but not by in situ hybridisation [30] nor by northern-blot [31]. Moreover, SF-1 knock-out mice do not show placental development nor placental steroid synthesis defects [29]. Ben-Zimra et al. have confirmed that SF-1 is dispensable in the placenta by showing that AP2 can substitute for SF-1 to induce P450scc expression in this tissue [32]. SF-1 expression has also been detected in the pituitary anlage, in the precursors of gonadotrope cells that control reproductive function and in the ventro-medial hypothalamus (VMH) which regulates the gonadotrope axis as well as some aspects of metabolism [33-35]. At last, SF-1 has also been detected in skin [36] where it is associated to steroidogenic enzymes [37-39] and in the spleen [31,40].

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