Document Detail

Progesterone increases manganese superoxide dismutase expression via a cAMP-dependent signaling mediated by noncanonical Wnt5a pathway in human endometrial stromal cells.
MedLine Citation:
PMID:  20685861     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Manganese superoxide dismutase (Mn-SOD), an antioxidant enzyme in the mitochondria, protects cells by scavenging superoxide radicals in human endometrial stromal cells (ESCs). Mn-SOD increases in ESCs during decidualization induced by progesterone.
OBJECTIVE: The present study investigated the molecular mechanism for Mn-SOD expression induced by progesterone in human ESCs.
METHODS: ESCs were incubated with medroxyprogesterone acetate (MPA; 10(-6) m) or dibutyryl-cAMP (0.5 mm) for 17 d. To determine whether a cAMP-dependent signaling pathway is involved in the MPA-induced Mn-SOD expression, ESCs were treated with H89, an inhibitor of cAMP-dependent protein kinase A. A chromatin immunoprecipitation assay was performed to examine the binding of cAMP-binding protein to the cAMP-response element on the Mn-SOD gene promoter. To examine the involvement of Wnt5a signaling, anti-Wnt5a antibodies were used to neutralize the Wnt5a activities.
RESULTS: Mn-SOD and Wnt5a mRNA levels and intracellular cAMP concentrations were significantly increased by MPA. These increases were accompanied by an increase in the mRNA expression of IGF-binding protein-1, a marker of decidualization. The increase in Mn-SOD mRNA levels by MPA or dibutyryl-cAMP was completely inhibited by H89. The chromatin immunoprecipitation assay revealed that MPA induced cAMP-binding protein binding with cAMP-response element on the Mn-SOD gene promoter. The increase in intracellular cAMP concentrations by MPA was completely inhibited by treatment with anti-Wnt5a antibodies. MPA treatment had no effects on β-catenin expression.
CONCLUSIONS: Progesterone increased Mn-SOD expression via a cAMP-dependent pathway in ESCs during decidualization. cAMP-dependent signaling stimulated by progesterone is mediated by noncanonical Wnt5a pathways that signal independently of β-catenin.
Aki Matsuoka; Fumie Kizuka; Lifa Lee; Isao Tamura; Ken Taniguchi; Hiromi Asada; Toshiaki Taketani; Hiroshi Tamura; Norihiro Sugino
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-04
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-05     Completed Date:  2010-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E291-9     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi, Ube, Japan.
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MeSH Terms
Bucladesine / metabolism,  pharmacology
Cells, Cultured
Chromatin Immunoprecipitation
Cyclic AMP / metabolism*
Endometrium / cytology,  drug effects,  metabolism*
Insulin-Like Growth Factor Binding Protein 1 / genetics,  metabolism
Medroxyprogesterone Acetate / metabolism,  pharmacology*
Middle Aged
Proto-Oncogene Proteins / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects*
Stromal Cells / drug effects,  metabolism
Superoxide Dismutase / genetics,  metabolism*
Wnt Proteins / genetics,  metabolism*
Reg. No./Substance:
0/IGFBP1 protein, human; 0/Insulin-Like Growth Factor Binding Protein 1; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/WNT5A protein, human; 0/Wnt Proteins; 362-74-3/Bucladesine; 60-92-4/Cyclic AMP; 71-58-9/Medroxyprogesterone Acetate; EC Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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