Endocrine Abstracts

The androgen receptor (AR) is the key transcription factor mediating androgen action during embryogenesis and postnatal life. Both adrenal and gonadal androgens act through the AR, which therefore has a major role both in female and male sexual maturation. Mutations in the X-chromosomally localized AR-gene have been associated with a variety of human disorders, namely in-born errors of male sexual differentiation as well as malignancy of endocrine organs such as prostate cancer, breast cancer, and laryngeal cancer. Inherited or early somatic mutations of the AR-gene are clinically associated with a wide spectrum of virilization deficits in karyotypic males, ranging from a complete female external phenotype (previously termed testicular feminization) over states of genital ambiguity to males with unequivocally male genitalia, but signs of slight undervirilization and/or infertility. Laboratory investigations in adulthood demonstrate a normal to high testosterone value together with high LH, thus the androgen sensitivity index (LH x T) is elevated. During infancy and childhood, laboratory investigations are much more difficult to interpret and require stimulation testing with human chorionic gonadotropin (hCG) for exclusion of an androgen biosynthesis disorder. Consequently, direct molecular genetic analysis of the AR gene has been widely accepted as a diagnostic tool for androgen insensitivity syndrome (AIS). However, the characterization of the underlying mutation in AIS does not allow a genotype-phenotype prediction in most instances of missense mutations. Therefore, appropriate counselling of affected individuals and their families is still difficult. New approaches with cDNA-microarray technology have allowed the identification of gene expression pattern controlled by the AR. With this knowledge, a better understanding of genital differentiation and an individual genotype-phenotype prediction may be possible in the future.