title: The subcellular defects in the androgen insensitivity syndrome.
abstract: The androgen insensitivity syndrome (AIS) was studied with consideration of the complexity of mechanisms involved on the intracellular level: testosterone (T) and dihydrotestosterone (DHT) receptors and the androgen-5 alpha-reductase (A5R). Five children with "normal" female external genitalia (group A) and three patients with variable forms of ambiguity (group B), ages 1 to 18 years, were studied. Tissue specimens from genital skin were analysed for the Kd- and N max-values of the cytosolic and nuclear T- and DHT-receptors, as well as for the Km- and Vmax-data of the tissue specific A5R. The enzyme analyses were performed with a kinetic method. Results show that patients from group A mainly lack action of the nuclear DHT receptor, combined with reduces binding capacity in the cytosol. T binding was poor in both, cytosolic and nuclear fractions, respectively. Results of group B proved to be more inhomogeneous, ranging from total absence of a DHT receptor to normal binding capacities in the nuclear fractions, accompanied by decreased cytosolic N max values for that ligand. T binding was poor in all patients of group B in the cytosolic and nuclear fractions, respectively. A5R was qualitatively normal in all patients examined, except one, but decreased enzyme activities could be observed in a wide range. In summary, the study confirms the complex mechanisms, presenting as AIS clinically. Moreover a close relationship between abnormalities of androgen receptor function and changes in A5R activity could be evaluated, thus confirming the recent theories about intracellular androgen action.
authors.forename: W
authors.initials: W
authors.lastname: Swoboda
authors.forename: K
authors.initials: K
authors.lastname: Herkner
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000293:Adolescent; D000728:Androgens / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance; D004700:Endocrine System Diseases / Q000378:metabolism*; D005837:Genitalia, Male / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007223:Infant; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure; D013577:Syndrome
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase