help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, M.-H.
Right arrow Articles by Tsai, S.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, M.-H.
Right arrow Articles by Tsai, S.-J.
(American Journal of Pathology. 2007;170:590-598.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060477

Aberrant Expression of Leptin in Human Endometriotic Stromal Cells Is Induced by Elevated Levels of Hypoxia Inducible Factor-1{alpha}

Meng-Hsing Wu*, Ko-Fan Chen{dagger}, Shih-Chieh Lin{dagger}, Chun-Wun Lgu{ddagger} and Shaw-Jenq Tsai{dagger}{ddagger}

From the Departments of Obstetrics & Gynecology* and Physiology{dagger} and the Institute of Basic Medical Sciences,{ddagger} National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China

Elevated expression of leptin in endometriotic tissue results in an increase in stromal cell proliferation and may contribute to the development of endometriosis. However, the underlying mechanism responsible for aberrant expression of leptin is not known. We hypothesize that aberrant expression of leptin in endometriotic stroma may be regulated by increased levels of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), the master transcription factor that controls gene expression in response to hypoxia. Herein we show that the mRNA and protein levels of HIF-1{alpha} were greater in ectopic endometriotic tissue compared with its eutopic counterpart. Exposure of eutopic endometrial stromal cells under hypoxic conditions or treated with desferrioxamine (DFO, chemical hypoxia) resulted in a time-dependent increase in leptin gene expression. A promoter activity assay demonstrated that HIF-1{alpha} induced leptin promoter activity after DFO treatment. Chromatin immunoprecipitation assay further demonstrated that binding of HIF-1{alpha} to leptin promoter was evident after DFO treatment. Finally, depletion of HIF-1{alpha} by short interference RNA abolished leptin expression in ectopic endometriotic stromal cells. Taken together, our data demonstrate that aberrant expression of leptin in ectopic endometriotic stromal cells is induced, at least in part, by an elevated level of HIF-1{alpha} in these cells, providing new insights into the etiology of endometriosis.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
C.-C. Hsu, C.-W. Lu, B.-M. Huang, M.-H. Wu, and S.-J. Tsai
Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and CCAAT/Enhancer-Binding Protein Mediate Prostaglandin E2-Induced Steroidogenic Acute Regulatory Protein Expression in Endometriotic Stromal Cells
Am. J. Pathol., August 1, 2008; 173(2): 433 - 441.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
B. Wang, I S. Wood, and P. Trayhurn
Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes
J. Endocrinol., July 1, 2008; 198(1): 127 - 134.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society for Investigative Pathology.