Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency
Adina F. Turcu,Aya T Nanba,Robert Chomic,Sunil K. Upadhyay,Thomas J. Giordano,James J. Shields,Deborah P. Merke,William E. Rainey,Richard J. Auchus +8 more
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TLDR
The data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess, and these steroids are elevated in both men and women with classic 21OHD.Abstract:
OBJECTIVE To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. DESIGN Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. METHODS We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. RESULTS Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. CONCLUSIONS All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess.read more
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Вроджена гіперплазія надниркових залоз внаслідок дефіциту 21-гідроксилази. Клінічні практичні настанови Ендокринологічного Товариства. Частина 1
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Lina Schiffer,Lise Barnard,Elizabeth S. Baranowski,Lorna C Gilligan,Angela E Taylor,Wiebke Arlt,Cedric H.L. Shackleton,Karl-Heinz Storbeck,Karl-Heinz Storbeck +8 more
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11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome.
Michael W O'Reilly,Michael W O'Reilly,Punith Kempegowda,Punith Kempegowda,Carl Jenkinson,Carl Jenkinson,Angela E Taylor,Angela E Taylor,Jonathan L. Quanson,Karl-Heinz Storbeck,Wiebke Arlt,Wiebke Arlt,Wiebke Arlt +12 more
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Steroidogenesis: Unanswered Questions.
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Intracrine androgen biosynthesis, metabolism and action revisited.
TL;DR: An overview of human C19 steroid biosynthesis including the production of 11-oxygenated androgens, their transport in circulation and uptake into peripheral tissues, and the mechanisms of intracrinology are conceptualised and reviewed.
References
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Journal ArticleDOI
Congenital adrenal hyperplasia
TL;DR: Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex as mentioned in this paper.
Journal ArticleDOI
Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline
Phyllis W. Speiser,Ricardo Azziz,Laurence S. Baskin,Lucia Ghizzoni,Terry W. Hensle,Deborah P. Merke,Heino F. L. Meyer-Bahlburg,Walter L. Miller,Victor M. Montori,Sharon E. Oberfield,Martin Ritzén,Perrin C. White +11 more
TL;DR: Clinical practice guidelines for congenital adrenal hyperplasia (CAH) recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests and recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.
Journal ArticleDOI
Androgens in teleost fishes
TL;DR: 11-Oxygenated androgens are generally more effective than T in stimulating secondary sexual characters, reproductive behaviour and spermatogenesis in teleost fishes but receptor-like binding has only reported for T and not for 11KT.
Journal ArticleDOI
Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Phyllis W. Speiser,Jakob Dupont,Deguang Zhu,Jorge Serrat,Miriam Buegeleisen,María Teresa Tusié-Luna,Martin Lesser,Maria I. New,Perrin C. White +8 more
TL;DR: The data suggest that most but not all of the phenotypic variability in 21-hydroxylase deficiency results from allelic variation in CYP21, which should be possible in most cases using the described strategy.