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

Hdl Handle:
http://hdl.handle.net/10147/207679
Title:
Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.
Authors:
Hogan, A M; Kennelly, R; Collins, D; Baird, A W; Winter, D C
Affiliation:
Institute for Clinical Outcomes Research and Education, St Vincent's University, Hospital, Dublin, Ireland.
Citation:
Br J Surg. 2009 Jul;96(7):817-22.
Journal:
The British journal of surgery
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207679
DOI:
10.1002/bjs.6612
PubMed ID:
19405165
Abstract:
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. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.
Language:
eng
MeSH:
Aged; Case-Control Studies; Cell Membrane; Colon/*drug effects; Cycloheximide/pharmacology; Estradiol/analogs & derivatives/*pharmacology; Estrogen Antagonists/pharmacology; Female; Gastrointestinal Motility/*drug effects; Humans; Male; Middle Aged; Muscle Contraction/*drug effects; Muscle, Smooth/*drug effects; Protein Synthesis Inhibitors/pharmacology
ISSN:
1365-2168 (Electronic); 0007-1323 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHogan, A Men_GB
dc.contributor.authorKennelly, Ren_GB
dc.contributor.authorCollins, Den_GB
dc.contributor.authorBaird, A Wen_GB
dc.contributor.authorWinter, D Cen_GB
dc.date.accessioned2012-02-01T10:34:44Z-
dc.date.available2012-02-01T10:34:44Z-
dc.date.issued2012-02-01T10:34:44Z-
dc.identifier.citationBr J Surg. 2009 Jul;96(7):817-22.en_GB
dc.identifier.issn1365-2168 (Electronic)en_GB
dc.identifier.issn0007-1323 (Linking)en_GB
dc.identifier.pmid19405165en_GB
dc.identifier.doi10.1002/bjs.6612en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207679-
dc.description.abstractBACKGROUND: 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. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshCell Membraneen_GB
dc.subject.meshColon/*drug effectsen_GB
dc.subject.meshCycloheximide/pharmacologyen_GB
dc.subject.meshEstradiol/analogs & derivatives/*pharmacologyen_GB
dc.subject.meshEstrogen Antagonists/pharmacologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGastrointestinal Motility/*drug effectsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshMuscle Contraction/*drug effectsen_GB
dc.subject.meshMuscle, Smooth/*drug effectsen_GB
dc.subject.meshProtein Synthesis Inhibitors/pharmacologyen_GB
dc.titleOestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.en_GB
dc.contributor.departmentInstitute for Clinical Outcomes Research and Education, St Vincent's University, Hospital, Dublin, Ireland.en_GB
dc.identifier.journalThe British journal of surgeryen_GB
dc.description.provinceLeinster-

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