An androgen receptor mutation causing androgen resistance in undervirilized male syndrome

Toshihiko Tsukada*, Masato Inoue, Sawako Tachibana, Yoshikatsu Nakai, Hiraku Takebe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


The molecular basis of androgen resistance was investigated in a patient with undervirilized male syndrome. Binding studies of the androgen receptors in the patient's genital skin fibroblasts revealed a normal binding capacity of 5α-dihydrotestosterone, although the affinity to androgen was slightly lower than the normal control value. The androgen binding of the patient's receptor showed a moderate thermal instability when the assay temperature was raised from 30 to 41 C. Nucleotide sequencing analysis of the androgen receptor gene revealed a single nucleotide substitution in exon F, resulting in an amino acid alteration from leucine (CTC) to phenylalanine (TTC) at position 789 within the steroid-binding domain of androgen receptor. When expressed in COS-7 cells, the mutant androgen receptor harboring phenylalanine at position 789 showed thermolabile androgen-binding properties similar to those observed in the patient's genital skin fibroblasts. Cotransfection experiments with an androgen-inducible reporter gene demonstrated a decreased transactivational capability of the mutant receptor. These results indicate that this point mutation modified the receptor function and caused androgen resistance in this patient. This mutation caused the mildest form of all androgen insensitivity syndromes ever examined for mutations in the androgen receptor gene.

Original languageEnglish
Pages (from-to)1202-1207
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Publication statusPublished - 1994 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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