Vázquez D M, López J F, Morano M I, Kwak S P, Watson S J, Akil H
Department of Pediatrics, Mental Health Research Institute, University of Michigan, Ann Arbor 48109, USA.
Endocrinology. 1998 Jul;139(7):3165-77. doi: 10.1210/endo.139.7.6095.
Two different types of corticoid receptor molecules bind circulating corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in the rat, corticosterone. During development, low corticosterone levels influence neurogenesis, and these effects are probably MR mediated. Three MR complementary DNA clones, alpha, beta, and gamma, have been identified in the rodent. All of these MR complementary DNA clones have identical coding regions, but differ significantly at the 5'-untranslated end. Although the functional significance of these three messenger RNA (mRNA) species remains unknown, one hypothesis is that they reflect the ability of the brain to regulate the expression of MR, allowing multiple factors to differentially control transcription in a tissue- and time-specific manner. To investigate this possibility, we examined the presence of these distinct mRNA forms in the developing rat hippocampus (HC). In situ hybridization with specific alpha, beta, and gamma complementary RNA probes was performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We found that there is differential expression of these forms in each of the HC subfields from infancy to adulthood. y expression appears to be associated with periods of cell birth and increased axonal sprouting. beta expression, on the other hand, may be best linked to periods of synaptogenesis, growth of commissural and associative terminal fields, and possibly active pruning. To explore the possibility that the differential gene expression may be related to corticosterone environment, adrenalectomy was performed. A rapid modulation of the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These findings suggest that the variation in expression and regulation during development of the multiple MR transcripts could reflect a complex pattern of developmental regulation that may involve a multitude of factors unique to each postnatal age and to the different neuronal populations within the hippocampal formation.
盐皮质激素受体（MR）和糖皮质激素受体。MR对大鼠体内的内源性糖皮质激素皮质酮具有最高亲和力。在发育过程中，低水平的皮质酮会影响神经发生，这些作用可能是由MR介导的。在啮齿动物中已鉴定出三个MR互补DNA克隆，α、β和γ。所有这些MR互补DNA克隆具有相同的编码区，但在5'-非翻译端有显著差异。尽管这三种信使RNA（mRNA）种类的功能意义尚不清楚，但一种假设是它们反映了大脑调节MR表达的能力，使多种因素能够以组织和时间特异性的方式差异控制转录。为了研究这种可能性，我们检测了发育中的大鼠海马体（HC）中这些不同mRNA形式的存在情况。在3、5、7、12、14、28、35和65日龄动物的HC中进行了与特异性α、β和γ互补RNA探针的原位杂交。我们发现，从婴儿期到成年期，这些形式在HC的每个亚区都有差异表达。γ表达似乎与细胞出生期和轴突发芽增加有关。另一方面，β表达可能与突触形成期、连合和联合终末场的生长以及可能的活跃修剪最相关。为了探索差异基因表达可能与皮质酮环境有关的可能性，进行了肾上腺切除术。观察到MR mRNA变体以年龄和位点特异性方式快速调节（14小时）。这些发现表明，多种MR转录本在发育过程中的表达和调节变化可能反映了一种复杂的发育调节模式，这可能涉及每个出生后年龄以及海马结构内不同神经元群体特有的多种因素。
