[Androgen receptor and insensitivity to androgens]

Androgen insensitivity syndromes are suspected in XY subjects with normal testosterone secretion presenting with absent or severely impaired androgen dependent sexual differentiation. Such clinical features suggest an abnormality of the androgen receptor, necessary step in the transmission of the hormonal message. The androgen receptor is a member of the steroid/thyroid nuclear receptors superfamily. It is a soluble protein of 919 amino acids, divided in independent functional domains responsible for the various functions of the receptor:hormone and DNA binding, and transcriptional activation. The highest concentration of androgen receptor is found, in both sexes, in tissues resulting from primary or secondary sexual differentiation. Cloning of the androgen receptor and use of molecular biology techniques have led to a new classification of androgen insensitivity syndromes. In complete forms (complete androgen insensitivity:CAI) the phenotype is feminine. In receptor negative CAI (Rc-: complete loss of hormone binding), molecular abnormalities include rare, partial or complete, deletions of the gene, or, more frequently, single point mutations in the hormone binding domain, leading to a functionally inactive receptor. Identification and characterization of these mutations provide valuable information regarding the functional importance of specific amino acids of the androgen receptor. In receptor positive CAI (RC+: conserved hormone binding capacity), abnormalities have been reported in the DNA binding domain (deletion of a zinc finger, single point mutations), but also in the hormone binding domain, thus distinguishing between the hormone binding activity and the transcriptional activation activity of this domain. Partial insensitivity syndromes are characterized by an ambiguous and extremely variable phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)