Desensitization of β2-adrenoceptor function in non-pregnant rat myometrium is modulated by sex steroids

Abstract

The effects of in vivo treatment with estrogen and progesterone on isoproterenol-induced uterine relaxation and β2-adrenoceptor (β2AR) mRNA production in non-pregnant rat myometrium were investigated. Whether homologous myometrial desensitization of β2AR function was dependent on or modulated by the two steroids was also examined. Estrogen treatment alone or in combination with progesterone reduced maximal relaxation (Emax) of isolated uterine strips subsequently challenged with isoproterenol whereas progesterone alone had no effect on this parameter. The reduction was accompanied by an enhanced β2AR mRNA concentration. The concentration of isoproterenol giving half-maximal relaxing response (EC50) increased following estrogen treatment and this effect was curbed by progesterone. Isoproterenol had no effect on β2AR transcription irrespective of the steroid regimes employed. Emax of isolated uterine strips was reduced following prolonged in vivo treatment with isoproterenol but the effect was found only when estrogen alone was administered concomitantly. Finally, in vivo treatment with isoproterenol increased EC50 of uterine strips subsequently stimulated with isoproterenol in vitro. This effect was independent of steroid treatment. We conclude that homologous desensitization of β2AR function in non-pregnant rat myometrium in terms of sensitivity (EC50) is independent of sex steroids but in terms of maximal response (Emax) occurs only in the presence of estrogen. We speculate whether progesterone withdrawal in connection with the well-known estrogen dominance at rat parturition may strengthen the desensitization induced by β2AR activation and thus contribute to the transformation of the uterus from a quiescent to a highly contractile organ.