Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal human subjects

The Journal of Clinical Endocrinology and Metabolism
E M FreelJohn M C Connell

Abstract

18-Hydroxycortisol (18-OHF) and 18-oxocortisol (18-oxoF) are derivatives of cortisol found in primary aldosteronism but whose origin and regulation in normal subjects are uncertain. 18-OHF can be synthesized by zona fasciculata 11-beta hydroxylase; 18-oxoF can only be produced by zona glomerulosa aldosterone synthase (AS). Stably transfected cell lines expressing either CYP11B1 (11beta-hydroxylase) or CYP11B2 (AS) were incubated with cortisol and other substrates over a range of concentrations. Both enzymes could synthesize 18-OHF from cortisol, but only AS could synthesize 18-oxoF. AS was more efficient than 11beta-hydroxylase at 18-hydroxylation. The apparent Michaelis-Menten constant (K(m)) of AS for cortisol was estimated to be 2.6 microm. In five patients with adrenal insufficiency maintained on hydrocortisone, urinary free cortisol and cortisone levels were high; 18-oxoF was detectable in all patients and 18-OHF in three. It is likely that the 18-oxygenated steroids were synthesized from circulating cortisol, either in the zona glomerulosa or at extraadrenal sites. In eight male volunteers, dexamethasone treatment decreased urinary excretion rates of free cortisol, cortisone, 18-OHF, and 18-oxoF, confirming dependence of ...Continue Reading

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Citations

Feb 9, 2016·Expert Opinion on Therapeutic Targets·Rita Bernhardt
Mar 27, 2007·Clinical Endocrinology·E M FreelJ M C Connell
May 17, 2014·The Lancet. Diabetes & Endocrinology·Silvia MonticonePaolo Mulatero
Dec 4, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Lina SchifferRita Bernhardt
Oct 30, 2016·Molecular and Cellular Endocrinology·Celso E Gomez-SanchezMax Wisgerhof
Nov 18, 2016·The Tohoku Journal of Experimental Medicine·Yasuhiro NakamuraHironobu Sasano
Apr 13, 2017·Pediatric Diabetes·Alfonso GalderisiEugenio Baraldi
Sep 15, 2017·European Journal of Endocrinology·Jacques W M LendersCelso E Gomez-Sanchez
Feb 23, 2007·Nature Clinical Practice. Endocrinology & Metabolism·Caroline Schirpenbach, Martin Reincke
Jan 13, 2012·The Journal of Clinical Endocrinology and Metabolism·Paolo MulateroFranco Veglio

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