Details

Autor(en) / Beteiligte

• Hornig, Nadine C
• Demiri, Jeta
• Rodens, Pascal
• Murga Penas, Eva Maria
• Caliebe, Almuth
• Eckstein, Anne Katrin
• Schweikert, Hans-Udo
• Audi, Laura
• Hiort, Olaf
• Werner, Ralf
• Kulle, Alexandra E
• Ammerpohl, Ole
• Holterhus, Paul-Martin

Titel

Reduced Androgen Receptor Expression in Genital Skin Fibroblasts From Patients With 45,X/46,XY Mosaicism

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2019-10, Vol.104 (10), p.4630-4638

Ort / Verlag

Washington, DC: Endocrine Society

Erscheinungsjahr

2019

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Context Molecular mechanisms causing the broad phenotypic diversity of external masculinization in individuals with 45,X/46,XY mosaicism are poorly understood. Objective Analysis of androgen receptor (AR) expression and function as a putative influencing factor for the genital phenotype in patients with 45,X/46,XY mosaicism. Design Measurement of AR mRNA expression levels, AR activity [DHT-mediated APOD (apolipoprotein D) induction] and cellular 45,X/46,XY ratios in genital skin fibroblasts from individuals with 45,X/46,XY mosaicism and male reference individuals, and determination of the external virilization scale from individuals with 45,X/46,XY mosaicism. Setting University hospital endocrine research laboratory. Patients or Other Participants: 30 genital skin fibroblast cultures (GFs) from male reference individuals and 15 GFs from individuals with 45,X/46,XY mosaicism. Intervention None Main Outcome Measures Determination of AR mRNA expression and AR activity in male reference GFs and 45,X/46,XY GFs and correlation of the obtained data with the cellular 45,X/46,XY ratios and the patients’ external virilization scale. Results In 6 of 15 45,X/46,XY GFs, AR mRNA expression and AR activity were significantly lower compared with those in the 46,XY reference GFs. In this subgroup of reduced AR mRNA expression, a positive trend was seen between AR mRNA expression and the percentage of XY-positive cells. Furthermore, we found a positive correlation between AR activity and the external virilization scale in the 15 45,X/46,XY GF samples (P = 0.03). Conclusion Our results suggest that AR expression and AR activity might influence the phenotypic variability seen in patients with 45,X/46,XY mosaicism. AR expression and function can be reduced in the genital target tissue of patients with 45,X/46,XY mosaicism, and AR function will correlate with the patients’ external virilization.