The androgenic effect of norethisterone and 5 alpha-norethisterone on the contractile response of the rat vas deferens to methoxamine and serotonin

Norethisterone (NET) and its metabolite 5 alpha-norethisterone (5 alpha-NET ) are competitors fdr the androgen receptor. The sensitivity of that vas de ferens to the contractile action of methoxamine and serotonin is regulated by hormonal and anatomical factors. The aim of this study was to evaluate t he ability of NET and 5 alpha-NET to induce the androgen-regulated contract ile response to methoxamine and serotonin in the epididymal and prostatic p ortions of rat vas deferens. Adult male rats either intact, castrated or st eroid-treated castrate were used. The contractility was recorded isometrica lly, and non-cumulative concentration-response curves to either methoxamine or serotonin were obtained. NET and 5 alpha-NET partially restored the sen sitivity to methoxamine and serotonin in epididymal portion of castrated ra ts. The maximal responses to both agonists were significantly higher than t hose observed in castrated rats, and significantly lower than the responses observed in either intact or androgen-treated castrated rats. The prostati c portion was less responsive to both agonists than the epididymal portion, in all groups but castrated rats, as castration induced sensitivity so bot h agonists. NET and 5 alpha-NET displayed a partial though similar androgen ic activity in the rat vas deferens. These results contrast with previous r eports where a decrease of androgenic effect due to the 5 alpha-reduction o f NET has been found. (C) 1999 Elsevier Science Inc.