GLUCOCORTICOID HORMONE RESISTANCE DURING PRIMATE EVOLUTION - RECEPTOR-MEDIATED MECHANISMS
GLUCOCORTICOID HORMONE RESISTANCE DURING PRIMATE EVOLUTION - RECEPTOR-MEDIATED MECHANISMS
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DOI：
10.1073/pnas.79.6.2036
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
LIPSETT, MB
中科院分区：
文献类型：
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作者：
CHROUSOS, GP;RENQUIST, D;LIPSETT, MB
新大陆猴血浆皮质醇总量和非蛋白质结合皮质醇浓度高于旧大陆灵长类和原猴。尿游离皮质醇排泄也明显增加。没有增加皮质醇效应的生理学证据。这些发现表明终末器官对糖皮质激素的抵抗。下丘脑-垂体-肾上腺轴对地塞米松的抑制有抵抗力，证实了这一点。为了研究这一现象，糖皮质激素受体进行了检查，在循环单核白细胞和培养的皮肤成纤维细胞从新的和旧的世界物种。受体含量在所有物种中是相同的，但新世界猴对地塞米松的结合亲和力显著降低。因此，这些物种对皮质醇作用的抗性是由于糖皮质激素受体的结合亲和力降低。这种假定的突变一定发生在旧世界和新世界灵长类动物的分叉之后（. apprx. 60倍106年前）和新世界灵长类动物相互转移之前（. apprx. 15倍106年前）。
The concentration of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. There is no physiological evidence of increased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action of cortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (.apprx. 60 .times. 106 yr ago) and before the diversion of the New World primates from each other (.apprx. 15 .times. 106 yr ago).