UMR788 Inserm and University Paris-Sud 11, Kremlin-Bicêtre, France.
Neuroscience. 2010 Mar 10;166(1):94-106. doi: 10.1016/j.neuroscience.2009.12.012. Epub 2009 Dec 16.
The recent molecular cloning of membrane receptors for progesterone (mPRs) has tremendous implications for understanding the multiple actions of the hormone in the nervous system. The three isoforms which have been cloned from several species, mPRalpha, mPRbeta and mPRgamma, have seven-transmembrane domains, are G protein-coupled and may thus account for the rapid modulation of many intracellular signaling cascades by progesterone. However, in order to elucidate the precise functions of mPRs within the nervous system it is first necessary to determine their expression patterns and also to develop new pharmacological and molecular tools. The aim of the present study was to profile mPR expression in the mouse spinal cord, where progesterone has been shown to exert pleiotropic actions on neurons and glial cells, and where the hormone can also be locally synthesized. Our results show a wide distribution of mPRalpha, which is expressed in most neurons, astrocytes, oligodendrocytes, and also in a large proportion of NG2(+) progenitor cells. This mPR isoform is thus likely to play a major role in the neuroprotective and promyelinating effects of progesterone. On the contrary, mPRbeta showed a more restricted distribution, and was mainly present in ventral horn motoneurons and in neurites, consistent with an important role in neuronal transmission and plasticity. Interestingly, mPRbeta was not present in glial cells. These observations suggest that the two mPR isoforms mediate distinct and specific functions of progesterone in the spinal cord. A significant observation was their very stable expression, which was similar in both sexes and not influenced by the presence or absence of the classical progesterone receptors. Although mPRgamma mRNA could be detected in spinal cord tissue by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization analysis did not allow us to verify and to map its presence, probably due to its relatively low expression. The present study is the first precise map of the regional and cellular distribution of mPR expression in the nervous system, a prior requirement for in vivo molecular and pharmacological strategies aimed to elucidate their precise functions. It thus represents a first important step towards a new understanding of progesterone actions in the nervous system within a precise neuroanatomical context.
最近，孕激素（mPRs）膜受体的分子克隆对理解该激素在神经系统中的多种作用具有重要意义。从多个物种中克隆出的三种同工型，mPRalpha、mPRbeta 和 mPRgamma，具有七个跨膜结构域，是 G 蛋白偶联的，因此可能解释了孕激素对许多细胞内信号级联的快速调制。然而，为了阐明 mPR 在神经系统中的精确功能，首先有必要确定它们的表达模式，同时也要开发新的药理学和分子工具。本研究的目的是研究 mPR 在小鼠脊髓中的表达模式，孕激素已被证明对神经元和神经胶质细胞有多种作用，并且该激素也可以在局部合成。我们的结果显示 mPRalpha 广泛表达，它存在于大多数神经元、星形胶质细胞、少突胶质细胞中，也存在于很大一部分 NG2(+)祖细胞中。因此，这种 mPR 同工型可能在孕激素的神经保护和促髓鞘形成作用中发挥主要作用。相反，mPRbeta 的分布更为局限，主要存在于腹角运动神经元和神经突中，与神经元传递和可塑性的重要作用一致。有趣的是，mPRbeta 不存在于神经胶质细胞中。这些观察结果表明，这两种 mPR 同工型介导了孕激素在脊髓中的不同和特定功能。一个重要的观察结果是它们非常稳定的表达，这种表达在两性中相似，不受经典孕激素受体存在与否的影响。虽然可以通过逆转录聚合酶链反应（RT-PCR）检测到脊髓组织中的 mPRgamma mRNA，但原位杂交分析不允许我们验证和绘制其存在的位置，可能是因为其表达相对较低。本研究首次精确绘制了 mPR 在神经系统中的区域性和细胞分布图谱，这是进行体内分子和药理学策略以阐明其精确功能的前提。因此，它是朝着在精确的神经解剖学背景下理解孕激素在神经系统中的作用迈出的重要一步。
