Androgen receptors and metabolism in cultured human fetal fibroblasts.
Testosterone metabolism and dihydrotestosterone (DHT) receptor activity were studied in fibroblasts cultured from genital and non-genital tissues of 8- to 22-week old human fetuses. As early as the eighth week of gestation, DHT receptor activity was detected in non-genital skin. The binding capacity (Bmax) was greater in genital skin fibroblasts (mean +/- SD = 474 +/- 32 moles x 10--18/micrograms DNA) than non-genital skin (mean +/- SD = 124 +/- 42 moles x 10(-18)/micrograms DNA). DHT receptor binding (Bmax) was found in fibroblasts derived from testes (112 moles x 10(-18)/micrograms DNA), but not intestine (less than 10 moles x 10(-18)/micrograms DNA). The DHT receptor activity of fetal skin fibroblasts of genital origin was similar to that of fibroblasts derived from the foreskin of normal newborns. DHT receptors from fetal and newborn fibroblast cultures had similar sedimentation coefficients in sucrose density gradient centrifugation, but there were small differences in their relative affinities for 17 beta-estradiol and cyproterone. Low, but detectable 5 alpha-reductase activity was observed at 8 weeks gestation in non-genital skin fibroblasts and was present in fibroblasts from a variety of tissues of older fetuses, including testes, kidneys and lungs. The highest 5 alpha-reductase activity of 210 pg/hour/micrograms DNA was found in fibroblasts cultured from clitoral tissue from a 10-week old fetus. In all but one specimen, the 5 alpha-reduced products were either DHT or 5 alpha-androstanedione. The demonstration of 5 alpha-reductase activity and specific DHT receptors in fetal tissues suggests that the intracellular mechanism for androgen action is present in the fetus, similar to that after birth.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D001667:Binding, Competitive; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005835:Genitalia / Q000196:embryology; D006801:Humans; D007668:Kidney / Q000196:embryology; D008168:Lung / Q000196:embryology; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012867:Skin / Q000196:embryology; D013739:Testosterone / Q000378:metabolism
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase