High impact information on Nr5a2

• FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA [1].
• LRH-1 induces human and mouse SR-BI promoter activity by binding to an LRH-1 response element in the promoter [2].
• Infection of undifferentiated granulosa cells with LRH-1 alone had no effect on estrogen production, progesterone production, or the expression of the LHr [3].
• Liver receptor homolog-1 stimulates the progesterone biosynthetic pathway during follicle-stimulating hormone-induced granulosa cell differentiation [3].
• We therefore provide evidence that LRH-1 plays an important role in the regulation of aromatase expression in Leydig cells [4].

Biological context of Nr5a2

• LRH-1 mRNA and protein were primarily localized to granulosa cells and luteinized follicles or newly formed corpora lutea (CLs) of immature and adult rats, and the levels of expression increased during eCG-hCG-induced follicular development and ovulation [5].
• In the functional CLs of pregnant rats, a biphasic change in LRH-1 mRNA content occurred throughout the gestation process, whereas LRH-1 protein was persistently detected during the entire pregnancy [5].
• These latter observations raised the possibility that FTF/LRH-1 may control target gene expression in granulosa cells of developing follicles [6].
• We show by in situ hybridization and LacZ expression in ovaries of transgenic mice bearing an FTF-promoter-LacZ fusion gene that FTF/LRH-1 is selectively expressed in granulosa cells of rat and mouse ovaries and is not present in theca cells or interstitial cells [6].
• In transient transfection assays using TM3 Leydig cells and TM4 Sertoli cells, a rat promoter II luciferase reporter construct was stimulated by cotransfection of LRH-1 expression vector [4].

Anatomical context of Nr5a2

• Stage-specific expression of LRH-1 in rat granulosa and luteal cells suggests a role for LRH-1 in the regulation of ovarian function [5].
• In the consecutive ovarian sections, expression of LRH-1 was approximately colocalized with that of P450arom in both tertiary and Graafian follicles and the functional CLs of pregnant rats [5].
• Liver receptor homologue 1 (LRH-1) is a member of the nuclear receptor superfamily originally found in liver cells [5].
• The colocalization of LRH-1 and aromatase to multiple testis cell types suggests that LRH-1 may have important effects on estrogen production, testis development, spermatogenesis, and testicular carcinogenesis [4].

Associations of Nr5a2 with chemical compounds

• LRH-1 participates in regulation of cholesterol metabolism and bile acid synthesis [5].
• SF-1 and FTF/LRH-1 were differentially regulated in vivo by estradiol, FSH and prolactin [6].
• However, combination of FSH stimulation and Ad-LRH-1 infection led to significantly greater progesterone production and increases in mRNA for p450 side-chain cleavage and 3beta-hydroxysteroid dehydrogenase than granulosa cells stimulated by FSH alone [3].
• In addition, the orphan nuclear receptor LRH-1 (liver receptor homologue-1) potentiated the sterol-dependent regulation of the sPLA(2) promoter by binding to an identified promoter element (TCAAGGCTG) [7].

Other interactions of Nr5a2

• Recent studies have shown that LRH-1 is even more highly expressed in the ovary, and LRH-1 has been implicated as a key transcriptional regulator of cytochrome P450 aromatase (P450arom) in vitro [5].

Analytical, diagnostic and therapeutic context of Nr5a2

• Using quantitative PCR our results show that FTF/LRH-1 message is expressed at higher levels in the ovary than in liver or other tissues analyzed [6].
• Mutation analysis showed that induction by LRH-1 in TM3 and TM4 cells requires an AGGTCA motif at position -90, to which LRH-1 bound in gel shift analysis [4].

References