PTGER1 and PTGER2 receptors mediate regulation of progesterone synthesis and type 1 11 β-hydroxysteroid dehydrogenase activity by prostaglandin E2 in human granulosa-lutein cells
PTGER1 and PTGER2 receptors mediate regulation of progesterone synthesis and type 1 11 β-hydroxysteroid dehydrogenase activity by prostaglandin E2 in human granulosa-lutein cells
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DOI：
10.1677/joe-07-0128
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发表时间：
2007-09-01
影响因子：
4
通讯作者：
Michael, A. E.
中科院分区：
文献类型：
--
作者：
Chandras, C.;Harris, T. E.;Michael, A. E.
在黄体化颗粒细胞中，前列腺素E-2（PGE（2））可以发挥促黄体作用，这显然是通过cAMP信号通路实现的。除了刺激孕酮的合成，PGE（2）还可以刺激生理性糖皮质激素（皮质醇）通过人颗粒体-叶黄素细胞中的1型11 β-羟基类固醇脱氢酶（11 β HSD 1）氧化成其非活性代谢物可的松。先前显示这些人卵巢细胞表达功能性G蛋白偶联的E系列前列腺素（PTGER）1、PTGER 2和PTGER 4受体，本研究的目的是描述PTGER 1和PTGER 2受体在介导PGE 2对人颗粒黄体细胞中类固醇生成和皮质醇代谢的作用中的作用。PGE（2）刺激的孕酮产生和cAMP积累的浓度依赖性增加（3000 nM PGE（2）分别为1.9 +/- 0.1和18.7 +/- 6.8倍）。虽然选择性PTGER 1拮抗剂SC 19220可以部分抑制对PGE（2）的类固醇生成反应（在1000 nM PGE（2）时为55.9 +/- 4.1%），但与AH 6809（一种混合PTGER 1/PTGER 2受体拮抗剂）共同处理，在所有测试浓度的PGE（2）下完全消除了孕酮合成的刺激，并抑制了cAMP积累的刺激。PGE（2）和布他前列素（一种首选的PTGER 2受体激动剂）均刺激11 β HSD 1浓度依赖性增加皮质醇氧化（在PGE 2和布他前列素浓度为1000 nM时，分别增加42.5 +/- 3.1和40.0 +/- 3.0%）。与SC 19220共同处理增强了PGE（2）和布他前列素刺激11 β HSD 1活性的能力（分别为30.2 +/-0.2%和30.5 +/- 0.6%），而与AH 6809共同处理完全消除了PGE（2）和布他前列素对11 β HSD 1的反应。这些发现表明，在人颗粒黄体细胞中，PGE（2）刺激孕酮产生和11 β HSD 1活性时，PTGER 2受体cAMP信号通路起作用。
In luteinizing granulosa cells, prostaglandin E-2 (PGE(2)) can exert luteotrophic actions, apparently via the cAMP signalling pathway. In addition to stimulating progesterone synthesis, PGE(2) can also stimulate oxidation of the physiological glucocorticoid, cortisol, to its inactive metabolite, cortisone, by the type 1 11 beta-hydroxysteroid dehydrogenase (11 beta HSD1) enzyme in human granulosa-lutein cells. Having previously shown these human ovarian cells to express functional G-protein coupled, E-series prostaglandin (PTGER)1, PTGER2 and PTGER 4 receptors, the aim of this study was to delineate the roles of PTGER1 and PTGER2 receptors in mediating the effects of PGE2 on steroidogenesis and cortisol metabolism in human granulosa-lutein cells. PGE(2)-stimulated concentration-dependent increases in both progesterone production and cAMP accumulation (by 1.9 +/- 0.1- and 18.7 +/- 6.8-fold respectively at 3000 nM PGE(2)). While a selective PTGER1 antagonist, SC19220, could partially inhibit the steroidogenic response to PGE(2) (by 55.9 +/- 4.1% at 1000 nM PGE(2)), co-treatment with AH6809, a mixed PTGER1/PTGER2 receptor antagonist, completely abolished the stimulation of progesterone synthesis at all tested concentrations of PGE(2) and suppressed the stimulation of cAMP accumulation. Both PGE(2) and butaprost (a preferential PTGER2 receptor agonist) stimulated concentration-dependent increases in cortisol oxidation by 11 beta HSD1 (by 42.5 +/- 3.1 and 40.0 +/- 3.0% respectively, at PGE2 and butaprost concentrations of 1000 nM). Co-treatment with SC19220 enhanced the ability of both PGE(2) and butaprost to stimulate 11 beta HSD1 activity (by 30.2 +/- 0.2 and 30.5 +/- 0.6% respectively), whereas co-treatment with AH6809 completely abolished the 11 beta HSD1 responses to PGE(2) and butaprost. These findings implicate the PTGER2 receptor cAMP signalling pathway in the stimulation of progesterone production and 11 beta HSD1 activity by PGE(2), in human granulosa-lutein cells.