Bogan Randy L, Murphy Melinda J, Stouffer Richard L, Hennebold Jon D
Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
Endocrinology. 2008 Nov;149(11):5861-71. doi: 10.1210/en.2008-0500. Epub 2008 Jul 17.
Prostaglandins in the corpus luteum (CL) reportedly serve as luteotropic and luteolytic agents. Based mainly on studies conducted in domesticated animals and rodents, prostaglandin E2 (PGE2) is generally considered a luteotropic factor, whereas uterine-derived prostaglandin F2alpha (PGF2alpha) initiates luteolysis. However, the role of prostaglandins in regulating primate luteal structure-function is poorly understood. Therefore, a comprehensive analysis of individual mRNA or proteins that are involved in PGE2 and PGF2alpha biosynthesis, metabolism, and signaling was performed using CL obtained at distinct stages of the luteal life span during the menstrual cycle in rhesus monkeys. Peak levels of proteins involved in PGE2 synthesis (prostaglandin-endoperoxide synthase 2, microsomal PGE2 synthase-1) and signaling (PGE2 receptor 3) occurred during periods corresponding to development and maintenance of the primate CL. Immunohistochemistry studies indicated that large luteal cells express PGE2 synthesizing and signaling proteins. Expression of PGE2 synthesizing and signaling proteins significantly decreased preceding the period of functional regression of the CL, which also coincided with increasing levels of PGF2alpha receptor protein expression within the large luteal cells. Moreover, significant levels of mRNA expression for several aldoketo reductase family members that synthesize PGF2alpha from other prostaglandins were observed throughout the rhesus macaque luteal phase, thus supporting the possibility of intraluteal PGF2alpha production. Collectively, our results indicate that there may be intraluteal synthesis and signaling of PGE2 during development and maintenance of the primate CL, followed by a shift to intraluteal PGF2alpha synthesis and signaling as the CL nears the time of luteolysis.
据报道，黄体（CL）中的前列腺素可作为促黄体生成素和黄体溶解剂。主要基于对家畜和啮齿动物的研究，前列腺素E2（PGE2）通常被认为是一种促黄体生成因子，而子宫来源的前列腺素F2α（PGF2α）则启动黄体溶解。然而，前列腺素在调节灵长类动物黄体结构功能中的作用却知之甚少。因此，利用恒河猴月经周期中黄体寿命不同阶段获得的黄体，对参与PGE2和PGF2α生物合成、代谢及信号传导的单个mRNA或蛋白质进行了全面分析。参与PGE2合成（前列腺素内过氧化物合酶2、微粒体PGE2合酶-1）和信号传导（PGE2受体3）的蛋白质峰值水平出现在与灵长类动物黄体发育和维持相对应的时期。免疫组织化学研究表明，大黄体细胞表达PGE2合成和信号传导蛋白。在黄体功能衰退期之前，PGE2合成和信号传导蛋白的表达显著下降，这也与大黄体细胞内PGF2α受体蛋白表达水平的增加相一致。此外，在整个恒河猴黄体期均观察到几种醛糖酮还原酶家族成员的mRNA表达水平显著升高，这些成员可从其他前列腺素合成PGF2α，从而支持了黄体内部产生PGF2α的可能性。总的来说，我们的结果表明，在灵长类动物黄体发育和维持过程中，可能存在黄体内部PGE2的合成和信号传导，随后随着黄体接近黄体溶解期，转变为黄体内部PGF2α的合成和信号传导。
