The human kidney is a progesterone-metabolizing and androgen-producing organ
The human kidney is a progesterone-metabolizing and androgen-producing organ
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DOI：
10.1210/jc.2002-021970
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发表时间：
2003-06-01
影响因子：
5.8
通讯作者：
Diederich, S
中科院分区：
文献类型：
--
作者：
Quinkler, M;Bumke-Vogt, C;Diederich, S
黄体酮(P)是体外人类矿皮质激素受体（MR）的有效拮抗剂。我们之前已经证明了肾中P的有效下游代谢。这种机制可能保护MR免受P的作用。在此，我们研究了类固醇生成酶在人体肾脏中的表达和功能活性。RT- PCR分析显示，5 α -还原酶1,5 α -还原酶、aldo-酮还原酶（AKR） 1C1、AKR1C2、AKR1C3、3 β -羟基类固醇脱氢酶（3 β - HSD） 2型和17 α -羟化酶/ 17,20-裂解酶（P450c17）均有表达。3 β - HSD 2型和P450c17的存在表明妊娠烯醇酮在肾脏中可以有效地转化为脱氢表雄酮（DHEA）和雄烯二酮。为了进一步研究这一点，我们用放射性标记的孕烯醇酮培养肾脏亚细胞组分。这导致孕烯醇酮有效形成脱氢表雄酮，表明P450c17具有17 α -羟化酶和17,20-裂解酶活性。放射性标记的脱氢表雄酮通过雄烯二酮、雄烯二醇和睾酮转化，显示3 β - HSD 2型活性和17 β - HSD活性。此外，睾酮转化为5 α -二氢睾酮是可检测的，表明5 α -还原酶活性。综上所述，我们证实了几种参与P下游代谢和雄激素合成的酶在人体肾脏中的表达和功能活性。这些发现可能对理解月经周期和怀孕期间的水分平衡以及高血压的性别差异至关重要。
Progesterone ( P) is a potent antagonist of the human mineralocorticoid receptor ( MR) in vitro. We have previously demonstrated effective downstream metabolism of P in the kidney. This mechanism potentially protects the MR from P action. Here, we have investigated the expression and functional activity of steroidogenic enzymes in human kidney. RT- PCR analysis demonstrated the expression of 5 alpha- reductase type 1, 5 alpha- reductase, aldo- keto- reductase ( AKR) 1C1, AKR1C2, AKR1C3, 3 beta- hydroxysteroid dehydrogenase ( 3 beta- HSD) type 2, and 17 alpha- hydroxylase/ 17,20- lyase ( P450c17). The presence of 3 beta- HSD type 2 and P450c17 indicated that conversion of pregnenolone to dehydroepiandrosterone ( DHEA) and to androstenedione may take place effectively in kidney. To investigate this further, we incubated kidney subcellular fractions with radiolabeled pregnenolone. This resulted in efficient formation of DHEA from pregnenolone, indicating both 17 alpha-hydroxylase and 17,20- lyase activities exerted by P450c17. Radiolabeled DHEA was converted via androstenedione, androstenediol, and testosterone, indicating both 3 beta- HSD type 2 activity and 17 beta- HSD activity. In addition, the conversion of testosterone to 5 alpha- dihydrotestosterone was detectable, indicating 5 alpha- reductase activity. In conclusion, we verified the expression and functional activity of several enzymes involved in downstream metabolism of P and androgen synthesis in human kidney. These findings may be critical to the understanding of water balance during the menstrual cycle and pregnancy and of sex differences in hypertension.