Soro A, Panarelli M, Holloway C D, Fraser R, Kenyon C J
MRC Blood Pressure Unit, Western Infirmary, Glasgow, Scotland, UK.
J Endocrinol Invest. 1995 Dec;18(11):833-9. doi: 10.1007/BF03349829.
The effect of a low dose of the gluco-corticoid receptor antagonist, RU486, was tested in spontaneously hypertensive (SHR) and in Sprague Dawley (SD) rats. In SD rats, RU486 (50 micrograms/day, 18 days) significantly increased growth rate and thymus weight, probably by antagonising the actions of endogenous glucocorticoid hormones. Blood pressure and plasma corticosterone levels were not affected by RU486 at this dose. In leucocytes, RU486 treatment in vivo reduced the number of glucocorticoid binding sites but did not affect binding affinity. In contrast, growth rate and thymus weight were not altered in SHR when treated with the same dose of RU486 for a longer period (60 days). Blood pressure was unaffected as were leucocyte glucocorticoid receptor characteristic. Glucocorticoid receptor binding characteristics for RU486 were similar for liver cytosol of SD and SHR. We conclude that the apparent difference in sensitivity to RU486 between strains is probably not due to differences in interaction of the antagonist with the glucocorticoid receptor but may be caused by differences in pharmacokinetics of RU486 between strains.
在自发性高血压大鼠（SHR）和斯普拉格-道利大鼠（SD）中测试了低剂量糖皮质激素受体拮抗剂RU486的作用。在SD大鼠中，RU486（50微克/天，共18天）显著提高了生长速率并增加了胸腺重量，这可能是通过拮抗内源性糖皮质激素的作用实现的。该剂量的RU486对血压和血浆皮质酮水平没有影响。在白细胞中，体内给予RU486治疗可减少糖皮质激素结合位点的数量，但不影响结合亲和力。相比之下，用相同剂量的RU486对SHR进行较长时间（60天）治疗时，生长速率和胸腺重量没有改变。血压未受影响，白细胞糖皮质激素受体特性也未受影响。SD大鼠和SHR大鼠肝脏胞质溶胶对RU486的糖皮质激素受体结合特性相似。我们得出结论，不同品系对RU486敏感性的明显差异可能不是由于拮抗剂与糖皮质激素受体相互作用的差异，而是可能由不同品系之间RU486的药代动力学差异引起的。
