The regulation by ovarian steroids of prostaglandin synthesis and prostaglandin-induced contractility in non-pregnant rat myometrium. Modulating effects of isoproterenol

Abstract

The objectives of the present study were to investigate the effects of the reproductive steroids oestradiol and progesterone on myometrial levels of cyclooxygenase-2 (COX-2) mRNA and PGF(2alpha) induced myometrial contractility and to study whether the effect of beta(2)-adrenoceptor stimulation by isoproterenol on the myometrium alters these parameters. Oestrogen treatment of ovariectomized rats increased myometrial COX-2 mRNA whereas PGF(2alpha) receptor (PGF(2alpha)-R) mRNA was unchanged following this treatment and maximal contractility (E(max)) of isolated uterine strips challenged with PGF(2alpha) was unaltered. Progesterone treatment alone decreased COX-2 mRNA in comparison with values obtained from oestrogen-treated animals, and in combination with oestrogen the enhancing effect of progesterone on COX-2 mRNA was curbed. EC(50) of uterine strips challenged with PGF(2alpha) increased following oestrogen treatment whereas this parameter was substantially decreased following progesterone treatment. When oestrogen was combined with isoproterenol infusion mRNA values of both COX-2 and PGF(2alpha)-R were reduced. Finally, when isoproterenol infusions were given in combination with both oestrogen and progesterone, PGF(2alpha)-R mRNA and E(max )were enhanced as compared with similar rats not having received isoproterenol. We conclude that oestrogen increases COX-2 mRNA production and subsequent prostaglandin synthesis in non-pregnant rat myometrium. We further conclude that in the oestrogen-dominated rat myometrium the relaxing effect of beta(2)-adrenoceptor stimulation involves attenuation of both prostaglandin synthesis and PGF(2alpha)-R expression. We finally conclude that in the presence of both oestrogen and progesterone this effect of beta(2)-adrenoceptor stimulation is restrained.