Aromatase activity in genital skin fibroblasts from normal and androgen-insensitive individuals.
Human genital skin fibroblasts were used to study aromatase activity by analysing the [3H]H2O released as [1 beta-3H]androstenedione is converted to oestrone. 4-Hydroxyandrostenedione was shown to be a competitive inhibitor of this aromatase activity, the concentration of inhibitor producing 50% inhibition being 1.29 nmol/l. Dexamethasone stimulated the enzyme complex in a dose-dependent manner with half-maximal stimulation at 11.5 nmol/l. A peak of induction occurred after 16 h of preincubation. Measurement of aromatase activity in normal cell strains provided a normal range for the Michaelis-Menten constant (Km) and the maximum velocity (Vmax) of 6.72 +/- 0.54 nmol/l and 215.3 +/- 33.9 fmol/mg protein per h (mean +/- S.E.M., n = 20) respectively. Km values obtained for partial and complete androgen insensitivity syndrome (PAIS and CAIS) patient cell strains were all within the normal range. The mean Vmax +/- S.E.M. in cell strains from patients with PAIS (n = 13) and CAIS (n = 11) were 127.4 +/- 19.2 and 54.8 +/- 19.3 fmol/mg protein per h respectively. Vmax values for patients with CAIS were significantly (P less than 0.001) lower than normal subjects. This suggests that aromatase expression in genital skin fibroblasts is androgen-dependent.
Stillman
S C
SC
Department of Child Health, University of Wales College of Medicine, Heath Park, Cardiff.
Evans
B A
BA
Hughes
I A
IA
D000728:Androgens / Q000494:pharmacology; D000735:Androstenedione / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D004970:Estrone / Q000378:metabolism; D005835:Genitalia / Q000201:enzymology; D006801:Humans; D011627:Puberty; D011944:Receptors, Androgen / Q000378:metabolism; D012867:Skin / Q000201:enzymology*
D000728:Androgens; D047072:Aromatase Inhibitors; D011944:Receptors, Androgen; D004970:Estrone; D000735:Androstenedione; D003907:Dexamethasone; D001141:Aromatase