TY - JOUR
T1 - Androgen receptors and metabolism in cultured human fetal fibroblasts
AU - Sultan, Charles
AU - Migeon, Barbara R.
AU - Rothwell, Stephen W.
AU - Maes, Marc
AU - Zerhouni, Nadia
AU - Migeon, Claude J.
PY - 1980/1
Y1 - 1980/1
N2 - 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/μg DNA) than non-genital skin (mean ±SD = 124 ± 42 moles x 10-18/μg DNA). DHT receptor binding (Bmax) was found in fibroblasts derived from testes (112 moles x 10-18/μg DNA), but not intestine (< 10 moles x 10-18/μg 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 17β-estradiol and cyproterone. Low, but detectable 5α-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 5α-reductase activity of 210 pg/hour/μg DNA was found in fibroblasts cultured from clitoral tissue from a 10-week old fetus. In all but one specimen, the 5α-reduced products were either DHT or 5α-androstanedione. The demonstration of 5α-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. SPECULATION: We have observed the conversion of testosterone into dihydrotestosterone (DHT) as well as DHT binding to a specific receptor in human fibroblasts cultured from a variety of tissues of fetal origin as early as 8 weeks gestation. It is speculated that the concentration of testosterone, the rate of formation of DHT and the concentration of androgen receptors each play a role in the differentiation of the external genitalia.
AB - 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/μg DNA) than non-genital skin (mean ±SD = 124 ± 42 moles x 10-18/μg DNA). DHT receptor binding (Bmax) was found in fibroblasts derived from testes (112 moles x 10-18/μg DNA), but not intestine (< 10 moles x 10-18/μg 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 17β-estradiol and cyproterone. Low, but detectable 5α-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 5α-reductase activity of 210 pg/hour/μg DNA was found in fibroblasts cultured from clitoral tissue from a 10-week old fetus. In all but one specimen, the 5α-reduced products were either DHT or 5α-androstanedione. The demonstration of 5α-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. SPECULATION: We have observed the conversion of testosterone into dihydrotestosterone (DHT) as well as DHT binding to a specific receptor in human fibroblasts cultured from a variety of tissues of fetal origin as early as 8 weeks gestation. It is speculated that the concentration of testosterone, the rate of formation of DHT and the concentration of androgen receptors each play a role in the differentiation of the external genitalia.
UR - http://www.scopus.com/inward/record.url?scp=0018921409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018921409&partnerID=8YFLogxK
U2 - 10.1203/00006450-198001000-00016
DO - 10.1203/00006450-198001000-00016
M3 - Article
C2 - 7360523
AN - SCOPUS:0018921409
SN - 0031-3998
VL - 14
SP - 67
EP - 69
JO - Pediatric research
JF - Pediatric research
IS - 1
ER -