Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.
Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.
复制标题
男性和女性尿液中非结合 19-去氧皮质酮的来源以及输注放射性标记 19-去氧皮质酮的代谢。
DOI：
10.1172/jci111834
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
MacDonald,PC
中科院分区：
文献类型：
--
作者：
Casey,ML;Guerami,A;Milewich,L;Gomez-Sanchez,CE;MacDonald,PC
众所周知，19-去甲-脱氧皮质酮 (19-去甲-DOC) 是一种有效的盐皮质类固醇，以游离（即非结合）形式存在于大鼠和人类的尿液中。在某些形式的高血压大鼠中，尿液中游离 19-nor-DOC 的水平与血压正常动物尿液中的水平相比有所增加。然而，尽管这种盐皮质类固醇在某些形式的高血压的发病机制中具有潜在的重要性，但对其起源或代谢部位知之甚少。在本研究中，我们评估了静脉输注的[3H]19-nor-DOC的代谢以及从血浆DOC形成19-nor-DOC的可能性。我们发现男性和女性静脉注射的[3H]19-nor-DOC 的代谢与DOC 相似，但有一些重要的例外。静脉输注的[3H]19-nor-DOC 的大多数放射性标记尿代谢物以葡萄糖醛酸苷形式从尿液中排出。以[3H]19-nor-DOC 形式输注的放射性很少，在尿液中以非缀合类固醇或磺基缀合类固醇形式回收。同时输注[3H]19-nor-DOC和[14C]DOC后，尿液中没有游离放射性标记的19-nor-DOC。尿液中[3H]19-nor-DOC的主要代谢物是19-nor-DOC-21-葡萄糖醛酸苷，而静脉输注的放射性标记的DOC很少或没有以放射性标记的DOC-葡萄糖醛酸苷的形式排出体外。我们还发现，静脉输注的[14C]DOC不会转化为尿液中的[14C]19-nor-DOC（葡萄糖醛酸苷），并且输注的[3H]19-nor-DOC的其他氚标记代谢物不含碳14。根据尿 19-nor-DOC（葡萄糖醛酸苷）的比活性计算，一名正常男性的 19-nor-DOC 生成率为 16 微克/天，本研究的两名女性为 10 微克/天。这些发现支持了以下观点：游离尿 19-nor-DOC 不是由血浆 DOC 形成的；它可以在肾脏中由 DOC 以外的前体形成，也可以在肾脏或尿液中由前体（例如 19-oic-DOC）非酶促形成。
It is known that 19-nor-deoxycorticosterone (19-nor-DOC) is a potent mineralocorticosteroid that is present in urine of rats and humans in a free, i.e., nonconjugated, form. In some forms of hypertension in rats, the levels of free 19-nor-DOC in urine are increased compared with those in urine of normotensive animals. Yet, despite the potential importance of this mineralocorticosteroid in the pathogenesis of certain forms of hypertension, little is known of its site of origin or metabolism. In the present investigation, we evaluated the metabolism of intravenously infused [3H]19-nor-DOC and the possibility that 19-nor-DOC was formed from plasma DOC. We found that the metabolism of [3H]19-nor-DOC infused intravenously in men and women was similar to that of DOC with important exceptions. The majority of the radiolabeled urinary metabolites of intravenously infused [3H]19-nor-DOC were excreted in urine as glucuronosides. Little radioactivity, infused as [3H]19-nor-DOC, was recovered in urine as nonconjugated or sulfoconjugated steroids. There was no free radiolabeled 19-nor-DOC in urine after the simultaneous infusion of [3H]19-nor-DOC and [14C]DOC. A major metabolite of [3H]19-nor-DOC in urine was 19-nor-DOC-21-glucuronoside, whereas little or no intravenously infused radiolabeled DOC was excreted as radiolabeled DOC-glucuronoside. We also found that intravenously infused [14C]DOC was not converted to urinary [14C]19-nor-DOC (glucuronoside) and that other tritium-labeled metabolites of infused [3H]19-nor-DOC contained no carbon-14. The production rate of 19-nor-DOC, computed from the specific activity of urinary 19-nor-DOC (glucuronoside), in one normal man was 16 micrograms/d and in the two women of this study, it was 10 micrograms/d. These findings are supportive of the proposition that free urinary 19-nor-DOC is not formed from plasma DOC; it may be formed in kidney from a precursor other than DOC or it may be formed nonenzymatically in kidney or urine from a precursor such as 19-oic-DOC.