TY - JOUR
T1 - Selective inhibition by secosteroids of 5α-reductase activity in human sex skin fibroblasts
AU - Zerhouni, Nadia A.
AU - Maes, Marc
AU - Sultan, Charles
AU - Rothwell, Stephen
AU - Mlgeon, Claude J.
N1 - Funding Information:
This work was supported by USPHS Research Grant AM-00180, Traineeship Grant 32-A&-07116 and Research and Career Award J-K06-AM-21355 (CJM). Dr. Zerhouni was supported by a Fellowship from the Algerian government. Dr. Maes was supported by a Research Fellowship of the Fogarty International Center 5-F05-TW02446. Dr. Sultan was supported by a Research Fellowship from the French government. We would like to thank Mrs. Jacqueline Kolb for expert technical assistance and Mrs. Barbara S. Mace for excellent secretarial help.
PY - 1979/3
Y1 - 1979/3
N2 - The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5α-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km, of the transformation of testosterone to 5α-reduced products was 387 pg/μg DNA/30 min and 234 × 10-9M, respectively. When the inhibitors were introduced in the assay, the 5α-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The K1for Compound I was 160 × 10-6M with a Vmax of 83 to 553 pg/Pg DNA/30 min. For Compound II, the Ki was 0.53 × 10-6M with a Vmax of 70 to 340 pg/yg DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for a3H-DHT and 3H-T for Compound I were 42.9 × 10-7M and 8.6 × 10-7M, respectively, whereas for Compound II, they were 10.6 × 10-7M and 4.8 × 10-7M.
AB - The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5α-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km, of the transformation of testosterone to 5α-reduced products was 387 pg/μg DNA/30 min and 234 × 10-9M, respectively. When the inhibitors were introduced in the assay, the 5α-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The K1for Compound I was 160 × 10-6M with a Vmax of 83 to 553 pg/Pg DNA/30 min. For Compound II, the Ki was 0.53 × 10-6M with a Vmax of 70 to 340 pg/yg DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for a3H-DHT and 3H-T for Compound I were 42.9 × 10-7M and 8.6 × 10-7M, respectively, whereas for Compound II, they were 10.6 × 10-7M and 4.8 × 10-7M.
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U2 - 10.1016/0039-128X(79)90004-7
DO - 10.1016/0039-128X(79)90004-7
M3 - Article
C2 - 442123
AN - SCOPUS:0018742170
SN - 0039-128X
VL - 33
SP - 277
EP - 285
JO - Steroids
JF - Steroids
IS - 3
ER -