Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome

Mahesh Appari, Ralf Werner, Lutz Wünsch, Gunnar Cario, Janos Demeter, Olaf Hiort, Felix Riepe, James D. Brooks, Paul Martin Holterhus*

*Korrespondierende/r Autor/-in für diese Arbeit
29 Zitate (Scopus)

Abstract

Androgen insensitivity syndrome (AIS) is the most common cause of disorders of sex development usually caused by mutations in the androgen receptor (AR) gene. AIS is characterized by a poor genotype-phenotype correlation, and many patients with clinically presumed AIS do not seem to have mutations in the AR gene. We therefore aimed at identifying a biomarker enabling the assessment of the cellular function of the AR as a transcriptional activator. In the first step, we used complementary DNA (cDNA) microarrays for a genome-wide screen for androgen-regulated genes in two normal male primary scrotal skin fibroblast strains compared to two labia majora fibroblast strains from 46,XY females with complete AIS (CAIS). Apolipoprotein D (APOD) and two further transcripts were significantly upregulated by dihydrotestosterone (DHT) in scrotum fibroblasts, while CAIS labia majora cells were unresponsive. Microarray data were well correlated with quantitative real-time polymerase chain reaction (qRT-PCR; R∈=∈0.93). Subsequently, we used qRT-PCR in independent new cell cultures and confirmed the significant DHT-dependent upregulation of APOD in five normal scrotum strains [13.5∈±∈8.2 (SD)-fold] compared with three CAIS strains (1.2∈±∈0.7-fold, p∈= 0.028; t test) and six partial androgen insensitivity syndrome strains (2∈±∈1.3-fold, p∈=∈0.034; t test). Moreover, two different 17ß-hydroxysteroid dehydrogenase III deficiency labia majora strains showed APOD induction in the range of normal scrotum (9.96∈±∈1.4-fold), supporting AR specificity. Therefore, qRT-PCR of APOD messenger RNA transcription in primary cultures of labioscrotal skin fibroblasts is a promising tool for assessing AR function, potentially allowing a function-based diagnostic evaluation of AIS in the future.

OriginalspracheEnglisch
ZeitschriftJournal of Molecular Medicine
Jahrgang87
Ausgabenummer6
Seiten (von - bis)623-632
Seitenumfang10
ISSN0946-2716
DOIs
PublikationsstatusVeröffentlicht - 01.06.2009

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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