EFFECT OF PREGNANCY ON RAT MYOMETRIAL BETA(2)-ADRENOCEPTOR MESSENGER-RNA AND ISOPROTERENOL-INDUCED RELAXATION OF ISOLATED UTERINE STRIPS

The altered myometrial contractile activity near term of pregnancy is partly due to changes in the responsiveness to catecholamines. Previou s experiments have basically been concerned with uterine adrenoceptor binding characteristics. Tn the present study we have evaluated total myometrial DNA, beta(2)-adrenoceptor mRNA and isoproterenol-induced re laxation of rat isolated uterine strips pre-contracted with potassium on days 0, 7, 14 and 21 of pregnancy and on day 5 post-partum. Total m yometrial DNA expressed per milligram wet tissue peaked at day 14 of p regnancy followed by a decrease at the end of gestation. This suggests that hyperplasia predominates in the growth of the uterus in early ge station, whereas hypertrophy may be more marked in late pregnancy. The concentration of beta(2)-adrenoceptor mRNA decreased linearly through out the gestational period (0.73 +/- 0.20 amol/mg wet tissue on day 0 vs 0.34 +/- 0.09 amol/mg wet tissue on day 21, P<0.05). Five days afte r parturition, at which time the uterus had returned to its pre-pregna nt weight, beta(2)-adrenoceptor mRNA was found to have increased 8-fol d (2.79 +/- 0.14 amol/mg wet tissue, P<0.05) as compared with day 21. The maximal effect of isoproterenol on pre-contracted uterine strips i n which alpha-receptors were blocked by phentolamine showed a similar decrease which on day 21 reached 67% of the day 0 level (P<0.001). EC5 0 values were unchanged in all groups except day 21 pregnant rats in w hich an increase was observed. One-way ANOVA with Bonferroni's t-test showed statistically significant differences only between the day 21 g roup and either the day 5 post-partum group or the day 14 pregnant gro up (P<0.05). The observed alteration in EC50 prior to the end oi gesta tion indicates that the system becomes less sensitive to beta(2)-adren ergic stimulation at this time. We conclude that a reduction of de nov o synthesis of beta(2)-adrenoceptors may play a role in contributing t o the increased myometrial activity at term. We further suggest that t he dramatic up-regulation of beta(2)-adrenoceptor mRNA postpartum may protect the fully involuted uterus against excessive contractions indu ced by oxytocin secreted during lactation.