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

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.

Epigenetic Repression of Androgen Receptor Transcription in Mutation-Negative Androgen Insensitivity Syndrome (AIS Type II).

Context: Inactivating mutations within the AR gene are present in only ~40% of individuals with clinically and hormonally diagnosed androgen insensitivity syndrome (AIS). Previous studies revealed the existence of an AR gene mutation-negative group of patients with AIS who have compromised androgen receptor (AR) function (AIS type II).

Objective: To investigate whether AIS type II can be due to epigenetic repression of AR transcription.