Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.
BACKGROUND
Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women.


METHODS
Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically.


RESULTS
Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation.


CONCLUSIONS
Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.
Hogan
A M
AM
Institute for Clinical Outcomes Research and Education, St Vincent's University Hospital, Dublin, Ireland.
Kennelly
R
R
Collins
D
D
Baird
A W
AW
Winter
D C
DC
D000368:Aged; D016022:Case-Control Studies; D002462:Cell Membrane; D003106:Colon / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D004965:Estrogen Antagonists; D011500:Protein Synthesis Inhibitors; D000077267:Fulvestrant; D004958:Estradiol; D003513:Cycloheximide