Document Detail


Regulation of NGFI-B/Nur77 gene expression in the rat ovary and in leydig tumor cells MA-10.
MedLine Citation:
PMID:  18163434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
NR4A1, also called NGFI-B in the rat, Nur77 in the mouse and TR3 in humans, belongs to the orphan nuclear steroid hormone receptor superfamily and is one of the immediate-early genes. In the endocrine organs, including the gonads, NGFI-B/Nur77 gene expression is rapidly induced by pituitary hormones. NGFI-B/Nur77 expression was found to be rapidly reduced by an estrogenic endocrine disrupter, diethylstilbestrol (DES) in theca interna cells of immature rat ovaries. DES treatment also triggered a rapid decrease of serum luteinizing hormone (LH) levels, suggesting that DES acts on the hypothalamo-pituitary axis to suppress LH secretion from the pituitary. The transcriptional regulation of NGFI-B/Nur77 by LH/human chorionic gonadotropin (hCG) or 8-bromoadenosine 3'-5'-cyclic monophosphate (8 Br-cAMP) was examined in mouse Leydig tumor cells MA-10. Luciferase assays using NGFI-B/Nur77 promoter constructs and electric mobility shift assays (EMSA) showed that NGFI-B/Nur77 gene expression was mediated through three of the four activator protein-1 (AP-1)-like sites, namely the -233 AP-1, -213 AP-1 and -69 AP-1 sites adjacent to the transcription start site of the NGFI-B/Nur77 promoter. We also demonstrated here that both the Jun family and cAMP-responsive element binding (CREB) proteins bind to the -233 AP-1 site, whereas the main binding protein to the -213 AP-1 site was CREB, and Jun family protein to the -69 AP-1 site, respectively. The rapid induction of NGFI-B/Nur77 gene expression by LH/hCG in MA-10 cells appears to be mediated by both CREB and Jun family proteins through the cAMP-protein kinase A (PKA) pathway.
Authors:
Yoshihiko Inaoka; Takashi Yazawa; Miki Uesaka; Tetsuya Mizutani; Kazuya Yamada; Kaoru Miyamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular reproduction and development     Volume:  75     ISSN:  1098-2795     ISO Abbreviation:  Mol. Reprod. Dev.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-02-28     Completed Date:  2008-07-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8903333     Medline TA:  Mol Reprod Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  931-9     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
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MeSH Terms
Descriptor/Qualifier:
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Animals
Cell Line, Tumor
Chorionic Gonadotropin / pharmacology
Cyclic AMP Response Element-Binding Protein / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
DNA-Binding Proteins / biosynthesis*
Diethylstilbestrol / pharmacology
Estrogens, Non-Steroidal / pharmacology
Female
Gene Expression Regulation, Neoplastic* / drug effects
Humans
Hypothalamo-Hypophyseal System / metabolism
Leydig Cell Tumor / metabolism*,  pathology
Luteinizing Hormone / pharmacology
Mice
Nuclear Receptor Subfamily 4, Group A, Member 1
Proto-Oncogene Proteins c-jun / metabolism
Rats
Receptors, Steroid / biosynthesis*
Response Elements
Theca Cells / metabolism*,  pathology
Transcription Factor AP-1
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Cyclic AMP Response Element-Binding Protein; 0/DNA-Binding Proteins; 0/Estrogens, Non-Steroidal; 0/NR4A1 protein, human; 0/Nr4a1 protein, mouse; 0/Nr4a1 protein, rat; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/Proto-Oncogene Proteins c-jun; 0/Receptors, Steroid; 0/Transcription Factor AP-1; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 56-53-1/Diethylstilbestrol; 9002-67-9/Luteinizing Hormone; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

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