Disease relevance of NR5A1

• Bovine theca cells were infected with recombinant adenovirus vectors over-expressing wild-type NR5A1 or NR5A1 mutants, in which one of the activating functions of this orphan nuclear receptor had been impaired [1].
• Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells [2].
• MATERIAL: Total RNA was extracted from 23 pituitary adenomas obtained by transsphenoidal surgery, and subjected to Northern blot analyses using cDNAs of bovine Ad4BP/SF-1, porcine FSH-beta, LH-beta and glycoprotein hormone-alpha (GPH-alpha) subunts as radiolabelled probes [3].

High impact information on NR5A1

• These results demonstrate that the balance between repressor and inducer function of DAX-1 and SF-1 are of critical importance in the regulation of adrenal aldosterone biosynthesis [4].
• Repression of DAX-1 and induction of SF-1 expression. Two mechanisms contributing to the activation of aldosterone biosynthesis in adrenal glomerulosa cells [4].
• Whereas Ang II was without effect on SF-1 expression, forskolin significantly increased SF-1 protein and mRNA levels in a cycloheximide-sensitive manner (to 167.4 +/- 16.6 and 173.1 +/- 25.1% of controls after 6 h, respectively, p < 0.01) [4].
• Induction of Ad4BP/SF-1, steroidogenic acute regulatory protein, and cytochrome P450scc enzyme system expression in newly established human granulosa cell lines [5].
• CONCLUSION: The regulation of the three NR5A1-controlled genes CYPA11, STAR, and INSL3 in luteinizing theca cells apparently is not dependent on NR5A1 activating functions AF-1 or AF-2 [1].

Biological context of NR5A1

• Two activating functions, AF-1 and AF-2, have been described to function in a cooperative manner to recruit transcriptional coactivators to the promoter regions of NR5A1-controlled genes [1].
• Activation of AF-1 here even appears to have an impairing effect on NR5A1 transcriptional activity, implying that up-regulation of NR5A1-controlled genes uses a different pathway [1].
• BACKGROUND: The orphan nuclear receptor NR5A1 (steroidogenic factor-1, SF-1) is a master regulator of tissue-specific gene expression in reproductive and steroidogenic tissues [1].

Anatomical context of NR5A1

• METHODS: The role of the NR5A1 activating functions AF-1 and AF-2 was studied in primary bovine theca cells [1].

Associations of NR5A1 with chemical compounds

• Unlike developmental/tissue-specific transcription of these genes which is regulated by a common transcription factor (SF-1), cAMP-dependent transcription of each steroid hydroxylase gene requires a different transcription factor [6].

References