XX MALES AND AMBIGUOUS GENITALIA: A LINK BETWEEN SRY AND ANDROGEN RECEPTOR (AR) GENE?

Abstract

Introduction. Most XX males, SRY positive, have a normal male phenotype. I some cases, XX males, SRY negative, are associated with ambiguous genitalia (AG). The aim of this study was to find out whether, in these patients, AR amount is diminished in target cells and whether partial androgen resistance is relevant to molecular abnormalities of the AR gene.

Patients and Method. Three XX males with AG were studied. PCR of the SRY gene, known to be equated to the testis determining gene, was negative. AR binding capacity (Bmax) and dissociation constant (Kd) of the A-AR complex were determined on genital skin fibroblasts by Scatchard analysis. PCR coupled with SSCP analysis was performed on all exons (4-8) encoding for the androgen-binding domain (ABD) of AR.

Results. Receptor-binding capacity was respectively 243, 206 and 162 fmol/mg DNA (N = 650 ± 200 fmol/mg DNA). Kd was respectively 1, 0.66 and 0.4 nM (N = 0.6 ± 0.3 nM). No band shifts were detected on the 5 exons studied. Known mutated exons of AR detected by SSCP were used as control.

Discussion. In patients with partial androgen insensitivity syndrome and diminished receptor binding capacity, a mutation has been reported within the ABD. In the 3 XX males, AG seems to be due to a low level of AR, without any detected mutation in the ABD. In these XX males, SRY negative, AG is relevant to a low level of expression of the AR gene. We suggest that the product of the SRY gene could thus be a transcriptional factor of the AR gene. Production of AR by AR-negative COS cells transfected by SRY gene is now under investigation.

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