[Regulation of aromatase in human choriocarcinoma cells].
To examine the mechanism regulating trophoblastic aromatase, we studied the effects of various agents on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in human choriocarcinoma JEG-3 cells. Aromatase activity was assessed by radioassay with [1 beta-3H] androstenedione. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Human chorionic gonadotropin (hCG) stimulated aromatase activity and increased the P-450arom concentration in a concentration-dependent (0.1-100 IU/ml) manner. Cholera toxin (CT), an adenylate cyclase activator, stimulated aromatase activity and the P-450arom concentration in a concentration-dependent (0.1-10ng/ml) and a time-dependent (12-72h) manner. 12-O-tetradecanoyl phorbol 13-acetate (TPA) (0.1-100ng/ml), a protein-kinase C activator, also stimulated aromatase activity and increased the P-450arom concentration. On the other hand, Ca2+ ionophore A23187, an agent increasing intracellular Ca2+ accumulation, inhibited aromatase activity and reduced the P-450arom concentration. The effects of CT, TPA and Ca2+ ionophore were additive. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in JEG-3 cells the signal transduction system modulates aromatase activity by changing the P-450arom concentration.
Kanno
H
H
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine.
Kitawaki
J
J
Maeda
K
K
Kim
T
T
Noguchi
T
T
Yamamoto
T
T
Okada
H
H
D001141:Aromatase / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D002822:Choriocarcinoma / Q000201:enzymology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology*
D006063:Chorionic Gonadotropin; D000001:Calcimycin; D002772:Cholera Toxin; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D013755:Tetradecanoylphorbol Acetate