Androgen dependent stimulation of aromatase activity in genital skin fibroblasts from normals and patients with androgen insensitivity.
OBJECTIVE
To measure the effect of androgens or aromatase activity as an index of androgen responsiveness in patients with androgen insensitivity.


METHODS
Genital skin fibroblasts were established in culture using primary skin explants obtained from normal males at the time of circumcision and from androgen insensitive patients who had surgery either for gonadectomy (complete androgen insensitivity syndrome) or for reconstruction of the external genitalia (partial androgen insensitivity syndrome).


METHODS
Foreskin samples were obtained at the time of circumcision in 27 normal males. Scrotal or labia majora skin was obtained at the time of surgery from 14 patients with the complete and 22 with the partial forms of the androgen insensitivity syndrome.


METHODS
Basal and stimulated levels of aromatase activity were measured in genital skin fibroblasts following preincubation with natural and synthetic, nonmetabolizable androgens.


RESULTS
Following a 48-hour preincubation with testosterone or dihydrotestosterone, there was a five to six-fold stimulation of aromatase activity in normal fibroblasts. Mibolerone, a synthetic androgen, produced similar results. The stimulatory effect was blocked by anti-androgens. Seven patients with partial androgen insensitivity, of whom four were either receptor deficient or showed a qualitative defect in androgen binding, had reduced mibolerone induced stimulation of aromatase activity. All ten patients with receptor negative complete androgen insensitivity had an absent response. There was no aromatase induction in a further three patients with complete androgen insensitivity who were receptor positive. Two siblings in the latter group had an exon deletion encoding for part of the DNA binding domain of the androgen receptor.


CONCLUSIONS
Androgens stimulate aromatase activity in genital skin fibroblasts from normals. The response is mediated via the androgen receptor and can be decreased or absent in patients with the androgen insensitivity syndrome. This may be a useful in-vitro marker of androgen responsiveness in such patients.
Stillman
S C
SC
Department of Child Health, University of Wales College of Medicine, Cardiff, UK.
Evans
B A
BA
Hughes
I A
IA
D000728:Androgens / Q000502:physiology*; D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D013196:Dihydrotestosterone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005835:Genitalia / Q000201:enzymology*; D006801:Humans; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000494:pharmacology; D045165:Testosterone Congeners / Q000494:pharmacology
D000728:Androgens; D011944:Receptors, Androgen; D045165:Testosterone Congeners; D013196:Dihydrotestosterone; D013739:Testosterone; D009277:Nandrolone; C100075:mibolerone; D001141:Aromatase