Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

Hdl Handle:
http://hdl.handle.net/10147/207506
Title:
Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.
Authors:
Hogan, A M; Collins, D; Sheehan, K; Zierau, O; Baird, A W; Winter, D C
Affiliation:
Institute for Clinical Outcomes Research and Education, St. Vincent's University , Hospital, Elm Park, Dublin 4, Ireland. Aislinghogan@yahoo.com
Citation:
Mol Cell Endocrinol. 2010 May 14;320(1-2):106-10. Epub 2010 Jan 28.
Journal:
Molecular and cellular endocrinology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207506
DOI:
10.1016/j.mce.2010.01.025
PubMed ID:
20109521
Abstract:
Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta isoform appears to play a predominant role in exerting non-genomic effects.
Language:
eng
MeSH:
Butadienes/pharmacology; Colon/*drug effects/*metabolism; Cycloheximide/pharmacology; Estradiol/analogs & derivatives/pharmacology; Estrogen Receptor beta/antagonists & inhibitors/*metabolism; Humans; Imidazoles/pharmacology; Muscle Contraction/drug effects; Muscle, Smooth/*drug effects/*metabolism; NG-Nitroarginine Methyl Ester/pharmacology; Nitriles/pharmacology; Phytoestrogens/chemistry/*pharmacology; Pyridines/pharmacology; Reproducibility of Results; Tissue Survival/drug effects
ISSN:
1872-8057 (Electronic); 0303-7207 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHogan, A Men_GB
dc.contributor.authorCollins, Den_GB
dc.contributor.authorSheehan, Ken_GB
dc.contributor.authorZierau, Oen_GB
dc.contributor.authorBaird, A Wen_GB
dc.contributor.authorWinter, D Cen_GB
dc.date.accessioned2012-02-01T10:29:45Z-
dc.date.available2012-02-01T10:29:45Z-
dc.date.issued2012-02-01T10:29:45Z-
dc.identifier.citationMol Cell Endocrinol. 2010 May 14;320(1-2):106-10. Epub 2010 Jan 28.en_GB
dc.identifier.issn1872-8057 (Electronic)en_GB
dc.identifier.issn0303-7207 (Linking)en_GB
dc.identifier.pmid20109521en_GB
dc.identifier.doi10.1016/j.mce.2010.01.025en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207506-
dc.description.abstractEpidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta isoform appears to play a predominant role in exerting non-genomic effects.en_GB
dc.language.isoengen_GB
dc.subject.meshButadienes/pharmacologyen_GB
dc.subject.meshColon/*drug effects/*metabolismen_GB
dc.subject.meshCycloheximide/pharmacologyen_GB
dc.subject.meshEstradiol/analogs & derivatives/pharmacologyen_GB
dc.subject.meshEstrogen Receptor beta/antagonists & inhibitors/*metabolismen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImidazoles/pharmacologyen_GB
dc.subject.meshMuscle Contraction/drug effectsen_GB
dc.subject.meshMuscle, Smooth/*drug effects/*metabolismen_GB
dc.subject.meshNG-Nitroarginine Methyl Ester/pharmacologyen_GB
dc.subject.meshNitriles/pharmacologyen_GB
dc.subject.meshPhytoestrogens/chemistry/*pharmacologyen_GB
dc.subject.meshPyridines/pharmacologyen_GB
dc.subject.meshReproducibility of Resultsen_GB
dc.subject.meshTissue Survival/drug effectsen_GB
dc.titleRapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.en_GB
dc.contributor.departmentInstitute for Clinical Outcomes Research and Education, St. Vincent's University , Hospital, Elm Park, Dublin 4, Ireland. Aislinghogan@yahoo.comen_GB
dc.identifier.journalMolecular and cellular endocrinologyen_GB
dc.description.provinceLeinster-

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