Cyclooxygenase enzyme expression and E series prostaglandin receptor signalling are enhanced in 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.
Smith
O P Milling
OP
Department of Reproductive and Developmental Sciences, The University of Edinburgh, Edinburgh, UK.
Jabbour
H N
HN
Critchley
H O D
HO
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000502:physiology; D000328:Adult; D000242:Cyclic AMP / Q000096:biosynthesis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D006801:Humans; D008183:Luteal Phase / Q000502:physiology; D008595:Menorrhagia / Q000201:enzymology* / Q000503:physiopathology*; D008875:Middle Aged; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4