Document Detail


Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome.
MedLine Citation:
PMID:  15598676     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by ovarian hyperandrogenism. Theca interna cells isolated from the ovaries of women with PCOS are characterized by increased expression of cytochrome P450 17alpha-hydroxylase (CYP17) [steroid 17alpha-hydroxylase/17,20 lyase (P450c17)], a steroidogenic enzyme obligatory for the biosynthesis of androgens. Augmented expression of the gene encoding P450c17 (CYP17) in PCOS theca has been attributed, in part, to differential transcriptional regulation of the CYP17 promoter in normal and PCOS cells. The present studies examine whether CYP17 gene expression is also posttranscriptionally regulated at the level of mRNA stability in normal and PCOS theca cells maintained in long-term culture. Determination of endogenous CYP17 mRNA half-life by pharmacological inhibition of transcription demonstrated that the half-life of CYP17 mRNA increased 2-fold in PCOS theca cells, compared with normal theca cells. Forskolin treatment also prolonged CYP17 mRNA half-life in both normal and PCOS theca cells. In vitro mRNA degradation studies demonstrated that the 5'-untranslated region confers increased stability to CYP17 mRNA in PCOS theca cells and showed that the 5'-untranslated region of CYP17 also confers forskolin-stimulated stabilization of CYP17 mRNA. These studies indicate that a slower rate of CYP17 mRNA decay contributes to increased steady-state mRNA accumulation and augmented CYP17 gene expression in PCOS theca cells.
Authors:
Jessica K Wickenheisser; Velen L Nelson-Degrave; Jan M McAllister
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-14
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  90     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-10     Completed Date:  2005-04-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1720-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Drive H166, Hershey, Pennsylvania 17033, USA. jmcallister@psu.edu
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions / genetics
5' Untranslated Regions / genetics
Adult
Cells, Cultured
Female
Gene Expression Regulation, Enzymologic / physiology*
Humans
Polycystic Ovary Syndrome / physiopathology*
RNA Stability / physiology*
RNA, Messenger / genetics
Steroid 17-alpha-Hydroxylase / genetics*
Theca Cells / cytology,  physiology*
Transfection
Grant Support
ID/Acronym/Agency:
HD33852/HD/NICHD NIH HHS; HD34449/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/5' Untranslated Regions; 0/RNA, Messenger; EC 1.14.99.9/Steroid 17-alpha-Hydroxylase

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


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