Walker B R, Williams B C, Edwards C R
Department of Medicine, Western General Hospital, University of Edinburgh, UK.
J Endocrinol. 1994 Jun;141(3):467-72. doi: 10.1677/joe.0.1410467.
11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) inactivates glucocorticoids and thereby modulates their access to both mineralocorticoid and glucocorticoid receptors. Since 11 beta-OHSD activity influences the biological responses of the hypothalamic-pituitary-adrenal axis, it might be regulated by components of this axis. We examined 11 beta-OHSD activity in adrenalectomized rats treated for 9 days with dexamethasone and with or without ACTH. Adrenalectomy and low-dose (2 micrograms/day) dexamethasone had no effect on 11 beta-OHSD activity in renal cortex, hippocampus or heart, and reduced enzyme activity in aorta. High-dose dexamethasone (50 micrograms/day) had no effect in renal cortex but increased enzyme activity by at least 50% in all other sites. This effect of dexamethasone was unaffected by the co-administration of ACTH. We also examined the metabolism of dexamethasone by 11 beta-OHSD in homogenized rat tissues. Only in kidney, in the presence of NAD rather than NADP, was dexamethasone converted to a more polar metabolite previously identified as 11-dehydrodexamethasone. We conclude that: dexamethasone induction of 11 beta-OHSD is tissue-specific, and includes vascular tissues and hippocampus but not kidney; this tissue-specificity may be explained by contrasting metabolism of dexamethasone by the isoforms of 11 beta-OHSD; fluctuations of glucocorticoid levels within the physiological range may not have a biologically significant effect on 11 beta-OHSD activity; and the inhibitory effect of ACTH, observed previously in humans, is likely to depend on the presence of intact adrenal glands.
11β-羟类固醇脱氢酶（11β-OHSD）使糖皮质激素失活，从而调节其与盐皮质激素受体和糖皮质激素受体的结合。由于11β-OHSD活性影响下丘脑-垂体-肾上腺轴的生物学反应，它可能受该轴各组成部分的调节。我们检测了用或不用促肾上腺皮质激素（ACTH）处理9天的肾上腺切除大鼠的11β-OHSD活性。肾上腺切除和低剂量（2微克/天）地塞米松对肾皮质、海马或心脏中的11β-OHSD活性无影响，但降低了主动脉中的酶活性。高剂量地塞米松（50微克/天）对肾皮质无影响，但使所有其他部位的酶活性至少增加50%。地塞米松的这种作用不受同时给予ACTH的影响。我们还检测了大鼠组织匀浆中11β-OHSD对地塞米松的代谢情况。仅在肾脏中，在地塞米松存在而不是烟酰胺腺嘌呤二核苷酸磷酸（NADP）存在的情况下，地塞米松被转化为一种极性更强的代谢产物，先前已鉴定为11-脱氢地塞米松。我们得出以下结论：地塞米松对11β-OHSD的诱导具有组织特异性，包括血管组织和海马，但不包括肾脏；这种组织特异性可能由11β-OHSD同工型对地塞米松的不同代谢来解释；生理范围内糖皮质激素水平的波动可能对11β-OHSD活性没有生物学上的显著影响；以及先前在人类中观察到的ACTH的抑制作用可能取决于肾上腺的完整性。
