Contribution of sex hormones to the sexually dimorphic response of colorectal motility to noxious stimuli in rats

Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this study was to determine whether sex hormones are major contributing factors for sex-dependent differences in neural components of the spinal defecation center. Colorectal motility was measured using an in vivo method under ketamine and α-chloralose anesthesia in rats. Capsaicin was administered into the colorectal lumen as noxious stimuli. Orchiectomy in male rats had no effect on the capsaicin-induced response of colorectal motility. However, in ovariectomized female rats, capsaicin administration enhanced colorectal motility, though intact female animals did not show enhanced motility. When estradiol was administered by using a sustained-release preparation in ovariectomized female rats, capsaicin administration did not enhance colorectal motility unless a GABA_A receptor antagonist was intrathecally administered to the lumbosacral spinal cord. These findings suggest that estradiol allowed the GABAergic neurons to operate in response to intracolonic administration of capsaicin. The operation of GABAergic inhibition by the action of estradiol could be manifested in male rats only when the effects of male sex hormones were removed by orchiectomy. Taken together, our results indicate that sex hormones contribute to the sexually dimorphic response in colorectal motility enhancement in response to noxious stimuli through modulating GABAergic pathways.NEW & NOTEWORTHY This study demonstrated that estradiol permits inhibitory regulation in the spinal defecation center not only in female rats but also in orchiectomized male rats. GABAergic pathways are likely involved in the effect of estradiol. This is the first report showing that sex hormones affect colorectal motility through the alteration of neural components of the regulatory pathways. Our findings provide a novel insight into pathophysiological mechanisms of defecation disorders related to changes in sex hormones.