Regulation of NGFI-B expression during the ovulatory process

Park, Jaeil; Park, Hyun-Jeong; Lee, Yu-Il; Seo, You‐Mi; Chun, Sang-Young

doi:10.1016/s0303-7207(03)00057-1

Cited by 37 publications

(27 citation statements)

References 41 publications

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“…Thus, there is strong evidence that the various NR4A family members can indeed compensate for one another in vivo. This likely includes the mammalian gonads, where two other NR4A family members, NR4A2 and NR4A3, are coexpressed with NR4A1 [24,43,44]. In support of this, we showed that NR4A2 and NR4A3 can activate the INSL3 promoter as well as NR4A1 (Fig.…”

Section: Discussionsupporting

confidence: 74%

The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells1

Robert¹,

Martin²,

Tremblay

2006

Biology of Reproduction

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Insulin-like 3 (INSL3) is a hormone produced by fetal and adult Leydig cells of the testis and by theca and luteal cells of the adult ovary. In males, INSL3 regulates testicular descent during fetal life, whereas in adults, it acts as a germ cell survival factor. In the ovary, INSL3 regulates oocyte maturation. Despite its importance for male sex differentiation and reproductive function in both sexes, very little is known regarding the molecular mechanisms that regulate Insl3 expression. So far, the nuclear receptor NR5A1 is the only transcription factor known to regulate the mouse Insl3 promoter in Leydig cells. NR5A1 by itself, however, cannot explain the spatiotemporal expression pattern of the Insl3 gene. In the present study, we have identified the orphan nuclear receptor NR4A1 as a novel regulator of INSL3 transcription in Leydig cells. Using RT-PCR, we found that Nr4a1 is coexpressed with Insl3 in purified Leydig cells and in several Leydig cell lines. Through detailed analyses of the mouse and human INSL3 promoter in Leydig cells, we have mapped a novel regulatory element located at -100 bp that is essential and sufficient to confer NR4A1 responsiveness. Consistent with a role for NR4A1 in Insl3 transcription, chromatin immunoprecipitation assays revealed that endogenous NR4A1 binds to the proximal Insl3 promoter in vivo. Finally, we found that NR4A1 is also implicated in cAMP-induced Insl3 transcription in Leydig cells. Taken together, our identification of NR4A1 as an important regulator of mouse and human INSL3 promoter activity helps us to better define the tissue-specific regulation of the INSL3 gene in gonadal cells.

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Section: Discussionsupporting

confidence: 74%

The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells1

Robert¹,

Martin²,

Tremblay

2006

Biology of Reproduction

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“…As shown in Fig. 1B, Nur77 as well as the other Nur77 family members, Nurr1 and Nor1, found in steroidogenic tissues (29,31) could activate a Ϫ1073 bp hHSD3B2 reporter construct (3-fold in MA-10 cells and 1.7-fold in H295R cells), whereas SF-1 and LRH-1 had no statistically significant effect (P Ͼ 0.05, by t test). This is probably due to the fact that these cells already contain significant levels of SF-1 and LRH-1 (9,15,46).…”

Section: Activation Of Hhsd3b2 Promoter Activity By Nur77 Factorsmentioning

confidence: 83%

The Human 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase Type 2 Promoter Is a Novel Target for the Immediate Early Orphan Nuclear Receptor Nur77 in Steroidogenic Cells

2005

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The human (h) 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase type 2 (3beta-HSD2) enzyme, encoded by the hHSD3B2 gene, is mainly found in gonads and adrenals. This enzyme catalyzes an essential early step in the biosynthesis of all classes of steroid hormones. The critical nature of the enzyme is supported by the occurrence of human syndromes that are associated with insufficient 3beta-HSD2 expression and/or activity. Although the need for a functional 3beta-HSD2 enzyme is indisputable, the molecular mechanisms that regulate HSD3B2 expression (both basal and hormone-induced) in steroidogenic cells remain poorly understood. A role for the Nur77 family of immediate-early orphan nuclear receptors in steroidogenesis has received recent interest. For example, Nur77 is present in gonads and adrenals, where its expression is robustly and rapidly induced by hormones that stimulate steroidogenic gene expression. Moreover, the expression patterns of Nur77 and at least one key steroidogenic gene (hHSD3B2) closely parallel one another. We now report that the hHSD3B2 promoter is indeed a novel target for Nur77 in both testicular Leydig cells and adrenal cells. We have mapped a novel response element located at -130 bp specific for Nur77 and not other orphan nuclear receptors (steroidogenic factor-1 and liver receptor homolog-1) previously shown to regulate hHSD3B2 promoter activity. This Nur77 element is essential and sufficient to confer Nur77 responsiveness to the hHSD3B2 promoter, and its mutation blunts basal and hormone-induced hHSD3B2 promoter activity in steroidogenic cells. We also show that Nur77 synergizes with all members of the steroid receptor coactivator family of coactivators on the hHSD3B2 promoter. Taken together, our identification of Nur77 as an important regulator of HSD3B2 promoter activity helps us to better define the tissue-specific and hormonal regulation of the HSD3B2 gene in steroidogenic cells.

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“…OTX2, a homeodomain protein shown to be expressed in murine GnRH neurons, is upregulated during GnRH neuronal development, increases GnRH promoter activity in GnRH-neuronal cell lines, and ensures reproductive competence [Diaczok et al, 2011]. Additionally, NRG1 and NR4A2, 2 genes important in neuronal differentiation and transcriptional regulation [Park et al, 2003], displayed elevated expression following GnRHa treatment (online suppl. Table 1).…”

Section: Gnrha-responsive Genes Act In Pathways Critical For the Hormmentioning

confidence: 99%

GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of the HPG Axis and Fertility

Hadžiselimović¹,

Gegenschatz‐Schmid²,

Verkauskas

et al. 2017

Sex Dev

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The gonadotropin-releasing hormone agonist (GnRHa; Buserelin) rescues fertility during adulthood in the majority of high infertility risk cryptorchid boys presenting with defective mini-puberty. However, the molecular events governing this effect are not understood. We report the outcome of an RNA profiling analysis of testicular biopsies from 4 operated patients who were treated with GnRHa for 6 months versus 3 operated controls who were not treated. GnRHa induces a significant transcriptional response, including protein-coding genes involved in pituitary development, the hypothalamic-pituitary-gonadal axis, and testosterone synthesis. Furthermore, we observed an increased abundance of long noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN, FENDRR, XIST, and HOTAIR. These data are consistent with the hypothesis that hypogonadotropic hypogonadism in boys with altered mini-puberty is the consequence of a profoundly altered gene expression program involving protein-coding genes and lncRNAs. Our results point to molecular mechanisms that underlie the ability of GnRHa to rescue fertility.

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Regulation of NGFI-B expression during the ovulatory process

Cited by 37 publications

References 41 publications

The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells1

The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells1

The Human 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase Type 2 Promoter Is a Novel Target for the Immediate Early Orphan Nuclear Receptor Nur77 in Steroidogenic Cells

GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of the HPG Axis and Fertility

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