Journal article

Publication year: 2012

Pages: E367-E375

Journal: The Journal of Clinical Endocrinology & Metabolism

Volume number: 97

Issue number: 3

ISSN: 0021-972X

Open access status: Bronze

DOI Link: https://doi.org/10.1210/jc.2011-1997

Publisher: Oxford University Press

Abstract: 

Background: 17-Hydroxyprogesterone (17-OHP) can be converted to dihydrotestosterone (DHT) via an alternative "backdoor" route that bypasses the conventional intermediates androstenedione and testosterone. In this backdoor pathway, 17-OHP is converted to 5 alpha-pregnane-3 alpha,17 alpha-diol-20-one (pdiol), which is an excellent substrate for the 17,20 lyase activity of CYP17A1 to produce androsterone.

Objective and Hypotheses: The objective of this study was to obtain evidence for the presence of the backdoor pathway in patients with 21-hydroxylase deficiency (21-OHD).

Methods: We compared urinary steroid hormone profiles determined by gas chromatography-mass spectrometry of 142 untreated 21-OHD patients (age range, 1 d to25.4 yr; 51 males) with 138 control subjects. The activity of the backdoor pathway was assessed using the ratios of the urinary concentrations of pdiol to those of the metabolites of the classic Delta(4) and Delta(5) pathways. In contrast to etiocholanolone, which originates almost exclusively from the classic pathways, androsterone may be derived additionally from the backdoor pathway. Therefore, the androsterone to etiocholanolone ratio can be used as an indicator for the presence of the backdoor pathway.

Results: Untreated 21-OHD subjects showed increased urinary ratios of pdiol to the Delta(4) and Delta(5) pathway metabolites and a higher androsterone to etiocholanolone ratio.

Conclusions: The elevated ratios of pdiol to the Delta(4) and Delta(5) pathway metabolites as well as the higher androsterone to etiocholanolone ratio in patients with 21-OHD indicate postnatal activity of the backdoor pathway with maximum activity during early infancy. Our data provide new insights into the pathophysiology of androgen biosynthesis of 21-OHD. (J Clin Endocrinol Metab 97: E367-E375, 2012)

Harvard Citation style: Kamrath, C., Hochberg, Z., Hartmann, M., Remer, T. and Wudy, S. (2012) Increased Activation of the Alternative "Backdoor" Pathway in Patients with 21-Hydroxylase Deficiency: Evidence from Urinary Steroid Hormone Analysis, The Journal of Clinical Endocrinology & Metabolism, 97(3), pp. E367-E375. https://doi.org/10.1210/jc.2011-1997

APA Citation style: Kamrath, C., Hochberg, Z., Hartmann, M., Remer, T., & Wudy, S. (2012). Increased Activation of the Alternative "Backdoor" Pathway in Patients with 21-Hydroxylase Deficiency: Evidence from Urinary Steroid Hormone Analysis. The Journal of Clinical Endocrinology & Metabolism. 97(3), E367-E375. https://doi.org/10.1210/jc.2011-1997