title: Estrogen and isoflavone attenuate stress-induced gastric mucosal injury by inhibiting decreases in gastric tissue levels of CGRP in ovariectomized rats.
abstract: We have previously reported that CGRP plays a critical role in the reduction of stress-induced gastric mucosal injury by increasing gastric prostacyclin (PGI(2)) levels in rats. Estrogen has been shown to increase the production of CGRP in sensory neurons. Isoflavone has estrogen-like effects and is referred to as a phytoestrogen. Thus, we hypothesized that estrogen and isoflavone might inhibit ovariectomy (OVX)-induced decreases in gastric tissue levels of CGRP, thereby attenuating gastric mucosal injury. We examined these possibilities in the present study. The administration of estradiol and isoflavone for 4 wk completely reversed OVX-induced decreases in CGRP mRNA levels of dorsal root ganglion neurons (DRGs) in rats. OVX-induced decreases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in rats were reversed by estradiol and isoflavone. Water-immersion restraint stress (WIR)-induced increases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were inhibited in ovariectomized rats. This inhibition was completely reversed by estradiol and was partially, but significantly, reversed by isoflavone. WIR-induced gastric mucosal injury was exacerbated by OVX, which was reversed by estradiol and isofolavone. In vitro experiments using DRGs isolated from rats demonstrated that neither estradiol nor isoflavone enhanced CGRP release from DRGs, but the former enhanced it in the presence of anandamide, an endogenous agonist for vanilloid receptor-1. These observations suggest that estrogen and isoflavone might inhibit OVX-induced decreases in CGRP levels in DRGs by promoting transcription, thereby contributing to the attenuation of stress-induced gastric mucosal injury in OVX rats.
authors.affiliation: Dept of Biodefense Medicine, Nagoya City Univ Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002478:Cells, Cultured; D063388:Endocannabinoids; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D008597:Menstrual Cycle / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004967:Estrogens; D007529:Isoflavones; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; C473894:fujiflavone P40; D004958:Estradiol; D015121:6-Ketoprostaglandin F1 alpha; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide