Hum. Reprod. Advance Access originally published online on January 30, 2007
Human Reproduction 2007 22(5):1450-1456; doi:10.1093/humrep/del503
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Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are enhanced in heavy menstruation
1 Department of Reproductive and Developmental Sciences, The University of Edinburgh 2 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, UK
3 To whom correspondence should be addressed at: Department of Reproductive and Developmental Sciences, The University of Edinburgh, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. E-mail: hilary.critchley{at}staffmail.ed.ac.uk
BACKGROUND: Although the mechanisms underlying the causes of heavy menstrual blood loss (MBL) remain to be elucidated, prostaglandins have been previously implicated. This study was initiated to elucidate a pattern of expression of the various components of the cyclooxygenase (COX)–prostaglandin signalling pathways present in the endometrium of women with normal and heavy MBLs.
METHODS: Endometrial biopsies were collected at different stages of the menstrual cycle from women who underwent measurement of MBL. Tissue was divided for either examination of gene expression by quantitative RT–PCR analysis or in vitro culture experimentation.
RESULTS: Analysis of gene expression demonstrated a significant elevation in expression of COX-1 and COX-2 mRNA in endometrium obtained from women with heavy MBL when compared with endometrium obtained from women with normal MBL. Tissue culture with PGE2 stimulation caused a significantly elevated production of cyclic AMP (cAMP) by endometrium of women with heavy MBL when compared with normal MBL. Expression of phosphodiesterase 4B, an enzyme involved in cAMP breakdown, was reduced in these same endometrial samples obtained from women with heavy MBL.
CONCLUSIONS: These data identify the E series prostaglandin receptors and their signalling pathways as potential therapeutic targets in the treatment of heavy menstruation.
Key words: cyclooxygenase/heavy menstruation/menorrhagia/prostaglandin receptors
Submitted on July 3, 2006; resubmitted on December 4, 2006; accepted on December 7, 2006.
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