Center for Neuroendocrinology, University of Massachusetts, Amherst, MA 01003, USA.
Neuroscience. 2011 Jan 13;172:55-65. doi: 10.1016/j.neuroscience.2010.10.051. Epub 2010 Oct 25.
Several lines of evidence suggest the existence of multiple progestin receptors that may account for rapid and delayed effects of progesterone in the CNS. The delayed effects have been long attributed to activation of the classical progestin receptor (Pgr). Recent studies have discovered novel progestin signaling molecules that may be responsible for rapid effects. These include progesterone receptor membrane component 1 (Pgrmc1), Pgrmc2, progestin and adipoQ receptor 7 (Paqr7) and Paqr8. The functions of these molecules have been investigated extensively in non-neural, but not in neural tissues, partly because it is unclear which are expressed in the brain and where they are expressed. To address these issues, we compared the distributions of mRNAs encoding Pgr, Pgrmc1, Pgrmc2, Paqr7 and Paqr8 using in situ hybridization with radiolabeled oligodeoxynucleotidyl probes in forebrain tissues of estradiol-treated female rats. We also examined the distribution of serpine mRNA binding protein 1 (Serbp1), a putative binding partner of Pgrmc1. Analyses of adjacent brain sections showed that the highest expression of mRNAs encoding Pgr, Pgrmc1, Pgrmc2 and Serbp1 was detected in several hypothalamic nuclei important for female reproduction. In contrast, expression patterns of Paqr7 and Paqr8 were low and homogeneous in the hypothalamus, and more abundant in thalamic nuclei. The neuroanatomical distributions of these putative progestin signaling molecules suggest that Pgrmc1 and Pgrmc2 may play roles in neuroendocrine functions while Paqr7 and Paqr8 are more likely to regulate sensory and cognitive functions.
有几条证据表明存在多种孕激素受体,这可能解释了孕激素在中枢神经系统中产生快速和延迟作用的原因。延迟作用长期归因于经典孕激素受体 (Pgr) 的激活。最近的研究发现了可能负责快速作用的新型孕激素信号分子。这些包括孕激素受体膜成分 1 (Pgrmc1)、Pgrmc2、孕激素和脂联素受体 7 (Paqr7) 和 Paqr8。这些分子的功能已在非神经组织中进行了广泛研究,但在神经组织中尚未进行研究,部分原因是不清楚哪些分子在大脑中表达以及它们在何处表达。为了解决这些问题,我们使用放射性标记的寡脱氧核苷酸探针,通过原位杂交比较了雌二醇处理的雌性大鼠前脑组织中编码 Pgr、Pgrmc1、Pgrmc2、Paqr7 和 Paqr8 的 mRNA 的分布。我们还检查了 serpine mRNA 结合蛋白 1 (Serbp1) 的分布,Serbp1 是 Pgrmc1 的一个假定结合伴侣。对相邻脑切片的分析表明,编码 Pgr、Pgrmc1、Pgrmc2 和 Serbp1 的 mRNA 的表达量在几个对女性生殖至关重要的下丘脑核中最高。相比之下,Paqr7 和 Paqr8 的表达模式在下丘脑较低且均匀,在丘脑核中更为丰富。这些假定的孕激素信号分子的神经解剖分布表明,Pgrmc1 和 Pgrmc2 可能在神经内分泌功能中发挥作用,而 Paqr7 和 Paqr8 更可能调节感觉和认知功能。