Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate.
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.
Johnson
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Section on Pediatric Endocrinology, Developmental Endocrinology Branch, NICHD, Bethesda, MD 20892, USA.
Brady
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Gold
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Chrousos
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D000818:Animals; D002144:Callithrix / Q000097:blood*; D004351:Drug Resistance; D005069:Evaluation Studies as Topic; D005938:Glucocorticoids / Q000097:blood / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D008253:Macaca mulatta / Q000097:blood*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*
D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D006854:Hydrocortisone