Johnson E O, Brady L, Gold P W, Chrousos G P
Section on Pediatric Endocrinology, Developmental Endocrinology Branch, NICHD, Bethesda, MD 20892, USA.
Steroids. 1996 Feb;61(2):69-73. doi: 10.1016/0039-128x(95)00195-v.
Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand, was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated, but ineffective, circulating cortisol.
糖皮质激素通过海马体中的盐皮质激素（MR）和糖皮质激素（GR）受体调节下丘脑 - 垂体 - 肾上腺轴的活性。此外，糖皮质激素会下调海马体中MR和GR mRNA及蛋白质的表达，推测这会降低其自身的作用。狨猴是一种新大陆灵长类动物，其特点是循环促肾上腺皮质激素（ACTH）和皮质醇水平异常高。这些动物对大量糖皮质激素相对不敏感，这归因于其GR对糖皮质激素的亲和力降低，以及该受体激活糖皮质激素反应性基因的能力受损。另一方面，盐皮质激素缺乏被归因于肾脏MR对皮质醇反应不佳，但对醛固酮反应正常。本研究的目的是检测狨猴（Callithrix jacchus jacchus）海马体中MR和GR mRNA的表达。总体而言，狨猴海马体所有亚区中MR和GR mRNA的稳态水平均升高，与典型的糖皮质激素敏感的旧大陆灵长类动物恒河猴（Macaca mulata）相比，这一点很明显。值得注意的是，狨猴齿状回和CA3区中GR mRNA水平极高。狨猴GR mRNA密度分布似乎也与恒河猴不同，也与先前报道的大鼠和人类不同。这些发现表明，狨猴海马体中MR和GR mRNAs存在代偿性升高，这似乎是靶组织对糖皮质激素抵抗以及循环皮质醇升高但无效导致的不适当下调的结果。
