Gonadotropin Regulation of NGFI-B Messenger Ribonucleic Acid Expression during Ovarian Follicle Development in the Rat*

Park, Jae-Il; Park, Hyun-Jeong; Choi, Hueng‐Sik; Lee, Keesook; Lee, Won-Kyo; Chun, Sang-Young

doi:10.1210/endo.142.7.8232

Cited by 39 publications

(5 citation statements)

References 40 publications

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“…It has been shown that ACTH, an anterior pituitary peptide hormone, rapidly induces Nur77 mRNA synthesis in the mouse adrenocortical tumor cell, Y1 (10), and more recently that PTH also induces Nur77 mRNA in primary mouse osteoblasts (37), and LH induces NGFI-B mRNA in rat ovarian follicle (38). Our results demonstrated that LH rapidly increased the expression of Nur77 mRNA in the Leydig cell line, K28.…”

Section: Discussionsupporting

confidence: 65%

LH Induces Orphan Nuclear Receptor Nur77 Gene Expression in Testicular Leydig Cells

et al. 2001

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The orphan nuclear receptor Nur77 (NR4A1) is a member of the nuclear receptor superfamily and plays an important role in the regulation of genes involved in steroidogenesis and cell death. Northern blot analysis revealed that the expression of Nur77 mRNA was increased after puberty in mouse testis, and hCG treatment of peripubertal animals induced this gene expression in the testis. Moreover, LH treatment induced a transient increase in Nur77 mRNA, and this induction was LH dose dependent in mouse Leydig tumor cell line, K28. Western blot analysis showed that LH transiently induced Nur77 protein. The protein kinase inhibitor H-89, bisindolymaleimide I, and wortmannin strongly inhibited this inductive effect of LH on Nur77 gene expression. Transient transfection assay demonstrated that LH significantly increased the Nur77 promoter-driven luciferase reporter activity in a dose-dependent manner, and LH also increased the activity of a luciferase reporter gene driven by a promoter containing multi copies of a Nur77-responsive element. Moreover, EMSA showed that Nur77 DNA-binding activity was increased in response to LH. Finally, overexpression of dominant negative Nur77 reduced LH-mediated progesterone biosynthesis. Taken together, these results demonstrate that LH induces Nur77 gene expression, and Nur77 may play an important role in the LH-mediated steroidogenesis in Leydig cells.

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Section: Discussionsupporting

confidence: 65%

LH Induces Orphan Nuclear Receptor Nur77 Gene Expression in Testicular Leydig Cells

et al. 2001

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“…C/EBPβ is rapidly induced in vivo by LH in granulosa cells is responsible for silencing the expression of genes after their early induction by LH . Egr‐1 and NGFI‐B bind genome regions rich in guanine and cytosine (GC‐rich) in the promoter region of numerous LH‐downstream genes . A complete luteinization process consists of three primary steps, that is , cell cycle arrest, tissue remodeling, and vascularization.…”

Section: Introductionmentioning

confidence: 99%

Melatonin and its receptor MT1 are involved in the downstream reaction to luteinizing hormone and participate in the regulation of luteinization in different species

Shi

et al. 2016

Journal of Pineal Research

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The functions of melatonin in preovulatory fluid remain elusive. In the current study, we observed that the extremely high level of expression of MT1 in mice granulosa cells was rapidly induced by hCG (equivalent LH) within 2 hours and this was referred as MT1 surge. In cumulus cells, serotonin N-acetyltransferase (SNAT) was also upregulated by hCG and led to elevated melatonin levels in ovarian follicle fluid. Melatonin application before MT1 surge significantly promoted embryo implantation, and this was probably attributed to a rise in progesterone levels in the serum. The mechanistic studies indicated that melatonin/MT1 (MLT/MT1) signaling remarkably improved the expression of corpus luteum marker genes, that is, Akr1c18 and Cyp11a1. High-throughput sequencing results suggested that extracellular matrix (ECM) receptor interaction, focal adhesion, and activation of PI3K/Akt pathway which are involved in granulosa cell luteinization might mediate the actions of MLT/MT1 signal. In addition, this effect on luteinization was compared in different species. It was verified that high melatonin levels exist in serum at estrum of cows and help to improve the first estrus fecundation rate. These results suggested that both melatonin and MT1 are involved in the downstream reaction of hCG (LH) and they play important roles in luteinization. These findings provide the novel information on the physiology of melatonin in animal reproduction.

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“…The orphan nuclear receptor NUR77 has received increased consideration lately as an important regulator of basal and hormone‐induced gene expression in steroidogenic cells, including in testicular Leydig cells. This stems in part from the fact that Nur77 expression is rapidly induced in these cells in response to LH/FSK/cAMP (Park et al, 2001; Song et al, 2001; Park et al, 2003; Li et al, 2004; Martin and Tremblay, 2005; Martin et al, 2008), which are well‐known regulators of Leydig cell gene expression and function. Although the regulation of Nur77 expression has been studied in other tissues and cell types, such as T cells, the mechanisms regulating its expression in Leydig cells remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with a role for the CaM pathway, we reported recently the expression of Ca 2+ /calmodulin kinase I (CaMKI) specifically in Leydig cells of the testis (Martin et al, 2008). Although Nur77 is rapidly and strongly induced in response to LH/forskolin/cAMP in Leydig cells (Park et al, 2001, 2003; Song et al, 2001; Li et al, 2004; Martin and Tremblay, 2005; Martin et al, 2008), where it regulates expression of several genes, surprisingly very little is known regarding the mechanisms regulating expression of Nur77 itself in these cells. There is only one recent report that revealed the implication of AP‐1 and CREB members in Nur77 promoter activity in Leydig cells (Inaoka et al, 2008).…”

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confidence: 99%

cAMP‐Induced Expression of the Orphan Nuclear Receptor Nur77 in MA‐10 Leydig Cells Involves a CaMKI Pathway

Martin

Boucher

El-Asmar

et al. 2009

Journal of Andrology

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The Nur77 (Nr4a1) gene, encoding the orphan nuclear receptor NUR77 (NR4A1), is an immediate early response gene whose expression is rapidly induced by a variety of physiologic stimuli. Nur77 is expressed in several organs, including the classic steroidogenic tissues: gonads and adrenal. In MA-10 Leydig cells, NUR77 has been shown to regulate expression of several genes involved in steroidogenesis and male sex differentiation. In Leydig cells, androgen biosynthesis is controlled primarily by the pituitary gonadotropin luteinizing hormone (LH) acting via its receptor (LH-R), which in turn activates the adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling pathway. Even though Nur77 expression is induced both at the mRNA and protein levels in response to LH/forskolin/cAMP in Leydig cells, the mechanisms involved remain largely unknown. Here, we report that cAMP-mediated induction of Nur77 expression at the protein, mRNA, and promoter levels in MA-10 cells involves different mechanisms. We found that increased NUR77 protein requires transcription and translation, whereas increased Nur77 mRNA does not require de novo protein synthesis, and would therefore rely on transcription factors already present in the cell. In addition, our detailed analysis of the Nur77 promoter in MA-10 cells revealed that distinct regulatory elements are involved in basal and cAMP-induced Nur77 transcription. Finally, we found that maximal cAMP-mediated increase in Nur77 promoter activity involves a Ca

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Gonadotropin Regulation of NGFI-B Messenger Ribonucleic Acid Expression during Ovarian Follicle Development in the Rat*

Cited by 39 publications

References 40 publications

LH Induces Orphan Nuclear Receptor Nur77 Gene Expression in Testicular Leydig Cells

LH Induces Orphan Nuclear Receptor Nur77 Gene Expression in Testicular Leydig Cells

Melatonin and its receptor MT1 are involved in the downstream reaction to luteinizing hormone and participate in the regulation of luteinization in different species

cAMP‐Induced Expression of the Orphan Nuclear Receptor Nur77 in MA‐10 Leydig Cells Involves a CaMKI Pathway

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