Disease relevance of Nr5a1

• Recombinant rat SF-1 protein expressed in Escherichia coli binds to this sequence, and antibodies raised against rat SF-1 abolish binding of both recombinant SF-1 and the nuclear protein from Y-1 and MA-10 cells [1].

High impact information on Nr5a1

• Gel shift experiments indicate the specific binding of the SF-1 and a potential SF-1-interacting factor to PARE I while a protein immunologically related to the cyclic AMP response element-binding protein interacts with PARE II [2].
• Altogether, these data establish the importance of the GnSE in the GnRH-R gene expression and reveal a novel role for SF-1 as a mediator of enhancer activity, a mechanism that might regulate other SF-1 target genes [3].
• We show that the GnSE activity (-1,135/-753) is mediated through a functional interaction with a proximal region (-275/-226) that includes the SF-1 response element [3].
• Transfection assays using an artificial promoter containing two SF-1 elements fused to a minimal PRL promoter indicate that SF-1 is crucial in this interaction [3].
• Proximal cis-acting elements, including steroidogenic factor 1, mediate the efficiency of a distal enhancer in the promoter of the rat gonadotropin-releasing hormone receptor gene [3].

Biological context of Nr5a1

• Stable transfection of murine MSCs with a transcription factor, steroidogenic factor-1, followed by treatment with cAMP almost recapitulated the properties of Leydig cells, including the production of testosterone [4].
• It is conceivable that the observed effects of DEHP on the expression of nuclear receptors SF-1 and PPARgamma are involved in the downregulation of steroidogenic factors and testosterone levels and thereby underlie the disturbed development of the male reproductive system [5].
• The significance of SF-1 in regulating target gene activation was supported by EMSA [6].
• Steroidogenic factor-1 (SF-1) (NR5A1) is an orphan nuclear receptor that plays a premier role in ovarian organogenesis [6].
• Changes in the spacing between the upstream Sp1 binding sites and the downstream SF-1/Egr-1 binding elements reduce the response to GnRH [7].

Anatomical context of Nr5a1

• Expression of SF-1 mRNA and protein in granulosa cells was verified by in situ hybridization, immunohistochemistry of ovarian sections, and immunocytochemistry of cultured rat granulosa cells [6].
• In LbetaT2 cells, a gonadotrope-derived cell line that expresses SF-1 endogenously, mutations in either the Sp1 or Egr-1 binding elements decrease GnRH responsiveness [7].
• Proper spatiotemporal expression of the MIS gene requires a specific combination of transcription factors, including the zinc finger factor GATA-4 and the nuclear receptor steroidogenic factor-1, which both colocalize with Müllerian inhibiting substance in Sertoli cells [8].
• This coexpression may imply SF-1 as a possible regulator of steroidogenesis in the hippocampus [9].
• Steroidogenic factor-1 (SF-1), an orphan nuclear receptor, was studied with respect to the expression of steroidogenic enzymes in the hippocampus of rat and marmoset, since SF-1 is a regulator of steroid biosynthesis in the gonads [9].

Associations of Nr5a1 with chemical compounds

• Additionally, we observed reduced mRNA expression of the nuclear receptor SF-1, which regulates certain steps in steroid synthesis, and reduced expression of the cryptorchidism-associated Insl-3 [5].
• The orphan nuclear receptor steroidogenic factor-1 regulates the cyclic adenosine 3',5'-monophosphate-mediated transcriptional activation of rat cytochrome P450c17 (17 alpha-hydroxylase/c17-20 lyase) [1].
• It is further shown that SF-1 can be phosphorylated in vitro by protein kinase A. This phosphorylation occurs at serine and threonine residues and results in decreased binding to the rP450c17 -58/-69 element [1].
• One, which we designated SF1, is a ubiquitous basal factor, and the other, SF2, is a T-cell-predominant phorbol myristate acetate-inducible factor [10].
• Polyphosphoinositides:stimulator of mitochondrial cholesterol side chain cleavage and possible identification as an adrenocorticotropin-induced, cycloheximide-sensitive, cytosolic, steroidogenic factor [11].

Physical interactions of Nr5a1

• Characterization of a steroidogenic factor-1-binding site found in promoter of sterol carrier protein-2 gene [12].

Regulatory relationships of Nr5a1

• Functional interactions, phosphorylation, and levels of 3',5'-cyclic adenosine monophosphate-regulatory element binding protein and steroidogenic factor-1 mediate hormone-regulated and constitutive expression of aromatase in gonadal cells [13].
• Steroidogenic factor-1 expression is transiently repressed and c-myc expression and deoxyribonucleic acid synthesis are induced in rat granulosa cells during the periovulatory period [14].

Other interactions of Nr5a1

• We further show that the effect of c-jun requires its DNA-binding domain and that c-jun interacts with Sf-1 and ERalpha and exerts synergistic effects on promoter activity with Sf-1, ERalpha, and Pitx1 [15].
• Consistent with this fact, we have recently shown that steroidogenic factor-1 (SF-1) mediates cAMP activation of the HDL receptor SR-BI gene [16].
• These results suggest the role of MIS in the regulation of follicular growth and the possible involvement of steroidogenic factor 1 and/or ER-beta in this molecular cascade may contribute to postnatal ovarian development [17].
• Furthermore, the expression levels of one of its transcriptional activators, steroidogenic factor 1, and ER-beta in granulosa cells of small growing follicles were higher in EB-treated ovaries than in the control ovaries [17].
• Steroidogenic factor-1 expression in marmoset and rat hippocampus: co-localization with StAR and aromatase [9].

Analytical, diagnostic and therapeutic context of Nr5a1

• In situ hybridization studies demonstrated that SF-1 was detected in the surface epithelium of rat ovaries, independent of age or gonadotropin treatment [18].
• Electrophoretic mobility shift assays demonstrated that Sp1, SF-1, and NF-Y enhanced SREBP-1a binding to SREs in the StAR promoter [19].
• Further, Northern blot and quantitative in situ hybridization studies revealed that significant amounts of SF-1 messenger RNA (mRNA) were present in EP-ROSE-179 cells but not in the other cell lines [18].
• StAR and aromatase-positive cells were strictly correlated with SF-1 as shown by computer-assisted confocal microscopy in double labelling experiments (immunohistochemistry and in situ hybridization) [9].
• SF-1 mRNA levels were measured in tissue dissections by ribonuclease protection assay [20].

References