Document Detail

Effects of medroxyprogesterone acetate on gene expression in myometrial explants from pregnant women.
MedLine Citation:
PMID:  20843944     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy, in part through controlling myometrial gene expression.
OBJECTIVE: The objective of the study was to use expression microarray and quantitative reverse transcriptase-PCR (qRT-PCR) validation to determine the changes in gene expression induced by prolonged exposure of human myometrium to a synthetic progestogen.
DESIGN: Myometrial explants, obtained at elective cesarean section (n=9), were maintained in culture, under 0.6 g tension, for 65 h in the presence of medroxyprogesterone acetate (100 nm) or vehicle. Expression array was performed using Illumina beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) by qRT-PCR.
RESULTS: The 114 significantly regulated transcripts were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004), and cytokine activity genes (P=0.008). Thirty-four transcripts were validated using qRT-PCR in explants obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes that have been well characterized as progesterone sensitive (IL-1B, IL-6, PTGS2, and GJA1). However, the top and sixth most down-regulated transcripts encoded two cytokines, IL-11 and IL-24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3- and 2.2-fold down-regulated, both P<0.001).
CONCLUSIONS: Medroxyprogesterone acetate controls expression of multiple genes in myometrium, including many that have not previously been characterized as progestogen regulated in this tissue, including IL-11 and IL-24. It is plausible that proteins encoded by some of these genes may have important but as yet uncharacterized effects in controlling human parturition.
Yolande Cordeaux; Mark Tattersall; D Stephen Charnock-Jones; Gordon C S Smith
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E437-47     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynaecology, University of Cambridge, Box 223, Cambridge CB2 0SW, United Kingdom.
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MeSH Terms
Cesarean Section
Contraceptive Agents, Female / pharmacology
Down-Regulation / drug effects
Gene Expression Regulation / drug effects*
Infant, Newborn
Interleukin-11 / genetics*
Interleukins / genetics*
Medroxyprogesterone Acetate / pharmacology*
Myometrium / cytology,  drug effects,  physiology*
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic / drug effects
Up-Regulation / drug effects
Reg. No./Substance:
0/Contraceptive Agents, Female; 0/Interleukin-11; 0/Interleukins; 0/interleukin-24; 71-58-9/Medroxyprogesterone Acetate

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