An alternative explanation of hypertension associated with 17伪-hydroxylase deficiency syndrome

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• 作者：David J. Morris ; Syed A. Latif ; Andrew S. Brem
• 关键词：17伪-Hydroxylase deficiency ; Kidney 11尾-HSD2-GALFs ; 3伪 ; 5伪-Tetrahydro-corticosterone ; 11尾-OH-(allo)-5伪-preganolone ; Intestinal flora
• 刊名：Steroids
• 出版年：January, 2014
• 年：2014
• 卷：79
• 期：Complete
• 页码：44-48
• 全文大小：655 K

文摘

The syndrome of 17伪-hydroxylase deficiency is due to the inability to synthesize cortisol and is associated with enhanced secretion of both corticosterone and 11-deoxy-corticosterone (DOC). In humans, corticosterone and its 5伪-Ring A-reduced metabolites are excreted via the bile into the intestine and transformed by anaerobic bacteria to 21-dehydroxylated products: 11尾-OH-progesterone or 11尾-OH-(allo)-5伪-preganolones (potent inhibitors of 11尾-HSD2 and 11尾-HSD1 dehydrogenase). Neomycin blocks the formation of these steroid metabolites and can blunt the hypertension in rats induced by either ACTH or corticosterone. 3伪,5伪-Tetrahydro-corticosterone, 11尾-hydroxy-progesterone, and 3伪,5伪-tetrahydro-11尾-hydroxy-progesterone strongly inhibit 11尾-HSD2 and 11尾-HSD1 dehydrogenase activity; all these compounds are hypertensinogenic when infused in adrenally intact rats.

Urine obtained from a patient with 17伪-hydroxylase deficiency demonstrated markedly elevated levels of endogenous glycyrrhetinic acid-like factors (GALFs) that inhibit 11尾-HSD2 and 11尾-HSD1 dehydrogenase activity (>300 times greater, and >400 times greater, respectively, than those in normotensive controls). Thus, in addition to DOC, corticosterone and its 5伪-pathway products as well as the 11-oxygenated progesterone derivatives may play a previously unrecognized role in the increased Na⁺ retention and BP associated with patients with 17伪-hydroxylase deficiency.