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MUCOSAL BIOLOGY

Estrogen and isoflavone attenuate stress-induced gastric mucosal injury by inhibiting decreases in gastric tissue levels of CGRP in ovariectomized rats

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto; and ²Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Submitted 15 March 2006 ; accepted in final form 26 September 2006

We have previously reported that CGRP plays a critical role in the reduction of stress-induced gastric mucosal injury by increasing gastric prostacyclin (PGI₂) 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-PGF₁, a stable metabolite of PGI₂, in rats were reversed by estradiol and isoflavone. Water-immersion restraint stress (WIR)-induced increases in gastric tissue levels of CGRP and 6-keto-PGF₁ 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.

phytoestrogen; prostacyclin; sensory neurons