Fernandes M S, Pierron V, Michalovich D, Astle S, Thornton S, Peltoketo H, Lam E W-F, Gellersen B, Huhtaniemi I, Allen J, Brosens J J
Institute of Reproductive and Developmental Biology, Wolfson & Weston Research Centre for Family Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
J Endocrinol. 2005 Oct;187(1):89-101. doi: 10.1677/joe.1.06242.
Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed 'progestin and adiponectin receptors' (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPRalpha and gamma and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPRalpha and beta transcripts. Interestingly, mPRalpha and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPRalpha. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPRalpha, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR.
孕酮的快速非基因组作用涉及女性生殖的许多方面。最近，已鉴定出鱼类膜孕激素受体（mPR）的三种人类同源物。我们将生物信息学分析与表达谱分析相结合，以进一步确定这些mPR在人类生殖组织中的作用。序列分析证实，mPR属于一个更大的、高度保守的蛋白质家族，称为“孕激素和脂联素受体”（PAQR）。将mPR转录本与两个相关的PAQR家族成员PAQRIII和PAQRIX在周期性子宫内膜和妊娠组织中的表达进行比较，发现表达水平和模式存在明显差异。例如，mPRα和γ以及PAQRIX的子宫内膜表达是周期依赖性的，而分娩的开始与子宫肌层mPRα和β转录本的显著减少有关。有趣的是，mPRα和PAQRIX在胎盘中表达最高，这两个基因的组织表达水平与核孕激素受体的表达水平呈负相关。系统发育分析表明，PAQRIX属于mPR蛋白质亚组。我们还验证了一种针对人类mPRα羧基末端产生的多克隆抗体。免疫组织化学分析表明，胎盘合体滋养层细胞中的免疫反应性比子宫内膜腺体或基质中的更强。数据表明mPRα以及可能的PAQRIX在特定生殖组织中具有重要功能作用，特别是那些核孕激素受体表达水平较低的组织。
