Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency: Implication for the backdoor pathway to dihydrotestosterone

Keiko Homma, Tomonobu Hasegawa, Toshiro Nagai, Masanori Adachi, Reiko Horikawa, Ikuma Fujiwara, Toshihiro Tajima, Ryoujun Takeda, Maki Fukami, Tsutomu Ogata

Research output: Contribution to journalArticle

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Abstract

Context: Although the "backdoor" pathway to dihydrotestosterone has been postulated in the fetal-to-early-infantile period of patients with cytochrome P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway remain limited. Objective: The objective of this study was to obtain clinical evidence for the presence of the backdoor pathway in PORD. Setting: This was a collaboration study between laboratories and hospitals. Subjects: Twenty-two Japanese patients with molecularly confirmed PORD and 1763 control subjects participated in this study. Intervention: Urine steroid profile analysis was performed by gas chromatography/mass spectrometry. In five patients and 776 control subjects, urine samples were obtained before 12 months of age. Main Outcome Measure: The main outcome measure was identification of a urine steroid(s) indicating the backdoor pathway. Results: In the PORD patients, pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased throughout the examined ages. Furthermore, etiocholanolone and 11-hydroxyandrosterone, which should originate almost exclusively from androstenedione in the conventional "frontdoor" pathway, were grossly normal or somewhat decreased since early infancy, whereas androsterone, which can be derived not only from androstenedione and dihydrotestosterone in the conventional frontdoor pathway but also from 5α-pregnane-3α, 17α-diol-20-one in the backdoor pathway, was increased during early infancy and remained grossly normal thereafter. Thus, the androsterone to etiocholanolone ratio was increased during early infancy and remained grossly normal thereafter. 5α-Pregnane-3α,17α-diol-20-one was elevated throughout the examined ages. Conclusions: The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the same period, suggests the presence of the backdoor pathway in PORD.

Original languageEnglish
Pages (from-to)2643-2649
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number7
DOIs
Publication statusPublished - 2006

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Antley-Bixler Syndrome Phenotype
Steroid hormones
Etiocholanolone
Dihydrotestosterone
Androsterone
Cytochrome P-450 Enzyme System
Oxidoreductases
Steroids
Urine
Hormones
Pregnanes
Androstenedione
Pregnanetriol
Outcome Assessment (Health Care)
Pregnanediol
Hospital Laboratories
Gas Chromatography-Mass Spectrometry
Gas chromatography
Mass spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency : Implication for the backdoor pathway to dihydrotestosterone. / Homma, Keiko; Hasegawa, Tomonobu; Nagai, Toshiro; Adachi, Masanori; Horikawa, Reiko; Fujiwara, Ikuma; Tajima, Toshihiro; Takeda, Ryoujun; Fukami, Maki; Ogata, Tsutomu.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 7, 2006, p. 2643-2649.

Research output: Contribution to journalArticle

Homma, Keiko ; Hasegawa, Tomonobu ; Nagai, Toshiro ; Adachi, Masanori ; Horikawa, Reiko ; Fujiwara, Ikuma ; Tajima, Toshihiro ; Takeda, Ryoujun ; Fukami, Maki ; Ogata, Tsutomu. / Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency : Implication for the backdoor pathway to dihydrotestosterone. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 7. pp. 2643-2649.
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abstract = "Context: Although the {"}backdoor{"} pathway to dihydrotestosterone has been postulated in the fetal-to-early-infantile period of patients with cytochrome P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway remain limited. Objective: The objective of this study was to obtain clinical evidence for the presence of the backdoor pathway in PORD. Setting: This was a collaboration study between laboratories and hospitals. Subjects: Twenty-two Japanese patients with molecularly confirmed PORD and 1763 control subjects participated in this study. Intervention: Urine steroid profile analysis was performed by gas chromatography/mass spectrometry. In five patients and 776 control subjects, urine samples were obtained before 12 months of age. Main Outcome Measure: The main outcome measure was identification of a urine steroid(s) indicating the backdoor pathway. Results: In the PORD patients, pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased throughout the examined ages. Furthermore, etiocholanolone and 11-hydroxyandrosterone, which should originate almost exclusively from androstenedione in the conventional {"}frontdoor{"} pathway, were grossly normal or somewhat decreased since early infancy, whereas androsterone, which can be derived not only from androstenedione and dihydrotestosterone in the conventional frontdoor pathway but also from 5α-pregnane-3α, 17α-diol-20-one in the backdoor pathway, was increased during early infancy and remained grossly normal thereafter. Thus, the androsterone to etiocholanolone ratio was increased during early infancy and remained grossly normal thereafter. 5α-Pregnane-3α,17α-diol-20-one was elevated throughout the examined ages. Conclusions: The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the same period, suggests the presence of the backdoor pathway in PORD.",
author = "Keiko Homma and Tomonobu Hasegawa and Toshiro Nagai and Masanori Adachi and Reiko Horikawa and Ikuma Fujiwara and Toshihiro Tajima and Ryoujun Takeda and Maki Fukami and Tsutomu Ogata",
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AU - Homma, Keiko

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AU - Nagai, Toshiro

AU - Adachi, Masanori

AU - Horikawa, Reiko

AU - Fujiwara, Ikuma

AU - Tajima, Toshihiro

AU - Takeda, Ryoujun

AU - Fukami, Maki

AU - Ogata, Tsutomu

PY - 2006

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N2 - Context: Although the "backdoor" pathway to dihydrotestosterone has been postulated in the fetal-to-early-infantile period of patients with cytochrome P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway remain limited. Objective: The objective of this study was to obtain clinical evidence for the presence of the backdoor pathway in PORD. Setting: This was a collaboration study between laboratories and hospitals. Subjects: Twenty-two Japanese patients with molecularly confirmed PORD and 1763 control subjects participated in this study. Intervention: Urine steroid profile analysis was performed by gas chromatography/mass spectrometry. In five patients and 776 control subjects, urine samples were obtained before 12 months of age. Main Outcome Measure: The main outcome measure was identification of a urine steroid(s) indicating the backdoor pathway. Results: In the PORD patients, pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased throughout the examined ages. Furthermore, etiocholanolone and 11-hydroxyandrosterone, which should originate almost exclusively from androstenedione in the conventional "frontdoor" pathway, were grossly normal or somewhat decreased since early infancy, whereas androsterone, which can be derived not only from androstenedione and dihydrotestosterone in the conventional frontdoor pathway but also from 5α-pregnane-3α, 17α-diol-20-one in the backdoor pathway, was increased during early infancy and remained grossly normal thereafter. Thus, the androsterone to etiocholanolone ratio was increased during early infancy and remained grossly normal thereafter. 5α-Pregnane-3α,17α-diol-20-one was elevated throughout the examined ages. Conclusions: The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the same period, suggests the presence of the backdoor pathway in PORD.

AB - Context: Although the "backdoor" pathway to dihydrotestosterone has been postulated in the fetal-to-early-infantile period of patients with cytochrome P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway remain limited. Objective: The objective of this study was to obtain clinical evidence for the presence of the backdoor pathway in PORD. Setting: This was a collaboration study between laboratories and hospitals. Subjects: Twenty-two Japanese patients with molecularly confirmed PORD and 1763 control subjects participated in this study. Intervention: Urine steroid profile analysis was performed by gas chromatography/mass spectrometry. In five patients and 776 control subjects, urine samples were obtained before 12 months of age. Main Outcome Measure: The main outcome measure was identification of a urine steroid(s) indicating the backdoor pathway. Results: In the PORD patients, pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased throughout the examined ages. Furthermore, etiocholanolone and 11-hydroxyandrosterone, which should originate almost exclusively from androstenedione in the conventional "frontdoor" pathway, were grossly normal or somewhat decreased since early infancy, whereas androsterone, which can be derived not only from androstenedione and dihydrotestosterone in the conventional frontdoor pathway but also from 5α-pregnane-3α, 17α-diol-20-one in the backdoor pathway, was increased during early infancy and remained grossly normal thereafter. Thus, the androsterone to etiocholanolone ratio was increased during early infancy and remained grossly normal thereafter. 5α-Pregnane-3α,17α-diol-20-one was elevated throughout the examined ages. Conclusions: The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the same period, suggests the presence of the backdoor pathway in PORD.

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