Hinko A, Soloff M S
Department of Surgery, Medical College of Ohio, Toledo 43699-1008.
Endocrinology. 1993 Oct;133(4):1511-9. doi: 10.1210/endo.133.4.8404589.
Oxytocin (OT) receptors (OTR) in rabbit amnion increase more than 200-fold at the end of gestation. In the present report, we studied the basis of this up-regulation. Incubation of amnion cells with cortisol (20 nM) for 24 h increased the amount of 125I-labeled OT antagonist bound by 16- to 18-fold. The effects of cortisol were dose and steroid dependent. Administration of glucocorticoid to pregnant does also increased the concentration of OTRs in amnion. The effects of cortisol in vitro were potentiated by the addition of forskolin (50 microM), so that OTR number increased by as much as 182 times. The effects of cortisol and forskolin, either separately or in combination, were inhibited by activation of protein kinase-C or coincubation with transforming growth factor-alpha (10 nM). Cyclosporin-A (5 microM) selectively inhibited cortisol-induced rises in the OTR concentration. The addition of cortisol to amnion cells increased OT-stimulated prostaglandin E2 (PGE2) release almost 100-fold; the combination of forskolin and cortisol increased the PGE2 response to OT about 5600 times. Judging from the greater effects on PGE2 release, these results suggest that forskolin and cortisol up-regulate the signal response mechanism to OT as well as the OTR concentration. The findings show that changes occurring in the amnion in vivo can be mimicked in vitro, and they elucidate the mechanism of up-regulation of OTR concentrations.
兔羊膜中的催产素（OT）受体（OTR）在妊娠末期增加超过200倍。在本报告中，我们研究了这种上调的基础。用皮质醇（20 nM）孵育羊膜细胞24小时，使125I标记的OT拮抗剂结合量增加了16至18倍。皮质醇的作用具有剂量和类固醇依赖性。给怀孕母兔注射糖皮质激素也增加了羊膜中OTR的浓度。加入福斯可林（50 microM）可增强皮质醇在体外的作用，使OTR数量增加多达182倍。单独或联合使用皮质醇和福斯可林的作用可被蛋白激酶-C激活或与转化生长因子-α（10 nM）共同孵育所抑制。环孢素-A（5 microM）选择性抑制皮质醇诱导的OTR浓度升高。向羊膜细胞中加入皮质醇可使OT刺激的前列腺素E2（PGE2）释放增加近100倍；福斯可林和皮质醇联合使用可使PGE2对OT的反应增加约5600倍。从对PGE2释放的更大影响来看，这些结果表明福斯可林和皮质醇上调了对OT的信号反应机制以及OTR浓度。研究结果表明，体内羊膜中发生的变化可以在体外模拟，并且阐明了OTR浓度上调的机制。
