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 PGE(2) 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.
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 PGE(2) 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.
Authors: D T Baird; S T Cameron; H O Critchley; T A Drudy; A Howe; R L Jones; R G Lea; R W Kelly Journal: Eur J Obstet Gynecol Reprod Biol Date: 1996-12 Impact factor: 2.435
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Authors: Jacqueline A Maybin; Sharon Battersby; Nikhil Hirani; Leonid L Nikitenko; Hilary O D Critchley; Henry N Jabbour Journal: Endocrinology Date: 2011-05-10 Impact factor: 4.736
Authors: Jacqueline A Maybin; Nikhil Hirani; Pamela Brown; Henry N Jabbour; Hilary O D Critchley Journal: J Clin Endocrinol Metab Date: 2011-06-15 Impact factor: 5.958
Authors: Linsay J Macdonald; Sheila C Boddy; Fiona C Denison; Kurt J Sales; Henry N Jabbour Journal: Reproduction Date: 2011-05-09 Impact factor: 3.906