Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism

• Published in: British journal of surgery Vol. 96; no. 7; pp. 817 - 822
• Main Authors: Hogan, A. M., Kennelly, R., Collins, D., Baird, A. W., Winter, D. C.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.07.2009; Wiley
• Subjects: Aged; Biological and medical sciences; Case-Control Studies; Cell Membrane; Colon - drug effects; Cycloheximide - pharmacology; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Female; Gastrointestinal Motility - drug effects; General aspects; Humans; Male; Medical sciences; Middle Aged; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Protein Synthesis Inhibitors - pharmacology; Human; Motility; Digestive system; Genomics; Gut; Estrogen; Ovarian hormone; Mechanism; Medicine; Membrane receptor; Treatment; Surgery; Plasma membrane; Inhibitor; Colon; Genome; Sex steroid hormone; Biological receptor
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1002/bjs.6612

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 17β‐oestradiol (n = 8) or bovine serum albumin (BSA)‐conjugated 17β‐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 17β‐oestradiol and BSA‐conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. Conclusion: Oestrogen decreases contractility in human colonic smooth muscle by a non‐genomic mechanism involving cell membrane coupling. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Insight into colonic transit times in females