Effect of pregnancy on rat myometrial beta 2-adrenoceptor mRNA 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. Previous experiments have basically been concerned with uterine adrenoceptor binding characteristics. In the present study we have evaluated total myometrial DNA, beta 2-adrenoceptor mRNA and isoproterenol-induced relaxation 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 myometrial DNA expressed per milligram wet tissue peaked at day 14 of pregnancy followed by a decrease at the end of gestation. This suggests that hyperplasia predominates in the growth of the uterus in early gestation, whereas hypertrophy may be more marked in late pregnancy. The concentration of beta 2-adrenoceptor mRNA decreased linearly throughout 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 after parturition, at which time the uterus had returned to its pre-pregnant weight, beta 2-adrenoceptor mRNA was found to have increased 8-fold (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 in 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). EC50 values were unchanged in all groups except day 21 pregnant rats in which an increase was observed. One-way ANOVA with Bonferroni's t-test showed statistically significant differences only between the day 21 group and either the day 5 post-partum group or the day 14 pregnant group (P < 0.05). The observed alteration in EC50 prior to the end of gestation indicates that the system becomes less sensitive to beta 2-adrenergic stimulation at this time. We conclude that a reduction of de novo synthesis of beta 2-adrenoceptors may play a role in contributing to the increased myometrial activity at term. We further suggest that the dramatic up-regulation of beta 2-adrenoceptor mRNA postpartum may protect the fully involuted uterus against excessive contractions induced by oxytocin secreted during lactation.
Engstrøm
T
T
Department of Internal Medicine and Endocrinology, University Hospital of Herlev, Copenhagen, Denmark.
Bratholm
P
P
Vilhardt
H
H
Christensen
N J
NJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009215:Myometrium / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D004247:DNA; D007545:Isoproterenol; D010646:Phentolamine