Engstrøm T, Bratholm P, Vilhardt H, Christensen N J
Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen, Denmark.
J Mol Endocrinol. 1998 Apr;20(2):261-70. doi: 10.1677/jme.0.0200261.
The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible interaction between the two systems has not been investigated. In the present study, long-term in vivo treatment of non-pregnant estrogen-primed rats with isoproterenol decreased maximal relaxation of isolated uterine strips challenged with isoproterenol. Increased EC50 values of similarly treated animals suggest that the coupling between receptor occupancy and contractile response was impaired. Since beta2AR mRNA levels were left unchanged, we conclude that the homologous desensitization to beta2 stimulation is not due to changes in beta2AR gene expression. OT infusion did not alter beta2AR mRNA levels or isoproterenol-induced relaxation of isolated uterine strips. Treatment with OT had no effect on the amount of myometrial OTR mRNA. We have previously found that OT down-regulates OTR in the non-pregnant rat myometrium, but this therefore does not appear to take place at the level of mRNA production. Isoproterenol treatment resulted in a three-fold increase in OTR mRNA. This was accompanied by a 91% rise in OTR binding and an augmented contractile response of isolated uterine strips to OT, suggesting that the increased production of mRNA reflects formation of active receptors. Neither OTR affinity nor EC50 of in vitro strips was affected by isoproterenol treatment. We conclude that stimulation of beta2AR causes heterologous up-regulation of OTR in the non-pregnant estrogen-primed rat myometrium.
九肽缩宫素（OT）通过与特定的质膜相关OT受体（OTR）相互作用诱导子宫肌层收缩，而刺激β2 - 肾上腺素能受体（β2AR）则导致松弛。子宫肌层对这两种激素的同源脱敏现象已有报道。然而，这两个系统之间可能的相互作用尚未得到研究。在本研究中，用异丙肾上腺素对未孕雌激素预处理的大鼠进行长期体内治疗，降低了用异丙肾上腺素刺激的离体子宫条的最大松弛度。同样处理的动物的EC50值增加表明受体占据与收缩反应之间的偶联受损。由于β2AR mRNA水平未发生变化，我们得出结论，对β2刺激的同源脱敏不是由于β2AR基因表达的改变。OT输注未改变β2AR mRNA水平或异丙肾上腺素诱导的离体子宫条松弛。OT处理对子宫肌层OTR mRNA的量没有影响。我们之前发现OT会下调未孕大鼠子宫肌层中的OTR，但因此这似乎不是在mRNA产生水平发生的。异丙肾上腺素处理导致OTR mRNA增加了三倍。这伴随着OTR结合增加91%以及离体子宫条对OT的收缩反应增强，表明mRNA产生的增加反映了活性受体的形成。异丙肾上腺素处理对体外条带的OTR亲和力和EC50均无影响。我们得出结论，刺激β2AR会导致未孕雌激素预处理的大鼠子宫肌层中OTR的异源上调。
