scholarly journals Genotype-Phenotype Analysis in Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency

2012 ◽  
Vol 97 (2) ◽  
pp. E257-E267 ◽  
Author(s):  
Nils Krone ◽  
Nicole Reisch ◽  
Jan Idkowiak ◽  
Vivek Dhir ◽  
Hannah E. Ivison ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase ◽  
Phenotype Analysis

scholarly journals Pubertal Presentation in Seven Patients with Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 741-742
Author(s):  
Jan Idkowiak ◽  
Stephen O'Riordan ◽  
Nicole Reisch ◽  
Ewa M. Malunowicz ◽  
Felicity Collins ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Clinical Endocrinology ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase

This article appears in The Journal of Clinical Endocrinology & Metabolism, published December 29, 2010, 10.1210/jc.2010-1607

Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study

The Lancet ◽  
2004 ◽  
Vol 363 (9427) ◽  
pp. 2128-2135 ◽  
Author(s):  
Wiebke Arlt ◽  
Elizabeth A Walker ◽  
Nicole Draper ◽  
Hannah E Ivison ◽  
Jon P Ride ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Analytical Study ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase ◽  
Androgen Synthesis

P450 Oxidoreductase Deficiency – A New Form of Congenital Adrenal Hyperplasia

2008 ◽  
pp. 67-81 ◽  
Author(s):  
Christa E. Flück ◽  
Amit V. Pandey ◽  
Ningwu Huang ◽  
Vishal Agrawal ◽  
Walter L. Miller
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase ◽  
New Form

scholarly journals Congenital adrenal hyperplasia and P450 oxidoreductase deficiency

2007 ◽  
Vol 66 (2) ◽  
Author(s):  
Nils Krone ◽  
Vivek Dhir ◽  
Hannah E. Ivison ◽  
Wiebke Arlt
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase

scholarly journals Alternative pathway androgen biosynthesis and human fetal female virilization

2019 ◽  
Vol 116 (44) ◽  
pp. 22294-22299 ◽  
Author(s):  
Nicole Reisch ◽  
Angela E. Taylor ◽  
Edson F. Nogueira ◽  
Daniel J. Asby ◽  
Vivek Dhir ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Androgen Receptor ◽  
Congenital Adrenal Hyperplasia ◽  
Nuclear Translocation ◽  
Alternative Pathway ◽  
Primary Cultures ◽  
Receptor Expression ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase ◽  
Female Genital

Androgen biosynthesis in the human fetus proceeds through the adrenal sex steroid precursor dehydroepiandrosterone, which is converted to testosterone in the gonads, followed by further activation to 5α-dihydrotestosterone in genital skin, thereby facilitating male external genital differentiation. Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency results in disrupted dehydroepiandrosterone biosynthesis, explaining undervirilization in affected boys. However, many affected girls are born virilized, despite low circulating androgens. We hypothesized that this is due to a prenatally active, alternative androgen biosynthesis pathway from 17α-hydroxyprogesterone to 5α-dihydrotestosterone, which bypasses dehydroepiandrosterone and testosterone, with increased activity in congenital adrenal hyperplasia variants associated with 17α-hydroxyprogesterone accumulation. Here we employ explant cultures of human fetal organs (adrenals, gonads, genital skin) from the major period of sexual differentiation and show that alternative pathway androgen biosynthesis is active in the fetus, as assessed by liquid chromatography–tandem mass spectrometry. We found androgen receptor expression in male and female genital skin using immunohistochemistry and demonstrated that both 5α-dihydrotestosterone and adrenal explant culture supernatant induce nuclear translocation of the androgen receptor in female genital skin primary cultures. Analyzing urinary steroid excretion by gas chromatography–mass spectrometry, we show that neonates with P450 oxidoreductase deficiency produce androgens through the alternative androgen pathway during the first weeks of life. We provide quantitative in vitro evidence that the corresponding P450 oxidoreductase mutations predominantly support alternative pathway androgen biosynthesis. These results indicate a key role of alternative pathway androgen biosynthesis in the prenatal virilization of girls affected by congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.

Pubertal Presentation in Congenital Adrenal Hyperplasia Due to P450 Oxidoreductase Deficiency.

2010 ◽  
pp. P2-747-P2-747
Author(s):  
J Idkowiak ◽  
S O'Riordan ◽  
EM Malunowicz ◽  
F Collins ◽  
M Kerstens ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
P450 Oxidoreductase
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