Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y.
The ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied by incubating the cells in the presence of labeled testosterone (T) or progesterone (P) to measure, respectively, the formation of dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells possess a significant 5 alpha-reductase activity, as shown by the considerable conversion of T into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester TPA, but not after differentiation induced by retinoic acid (RA). The 5 alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP. In undifferentiated cells, this conversion was about 8 times higher than that of T into DHT. Under the influences of TPA and RA, the formation of DHP followed the same pattern observed for the formation of DHT. SH-SY5Y cells also appear to possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3 alpha-diol. This enzymatic activity is not altered following TPA-induced differentiation and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells.
Melcangi
R C
RC
Department of Endocrinology, University of Milano, Italy.
Maggi
R
R
Martini
L
L
D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D001711:Biotransformation; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013196:Dihydrotestosterone; D004092:20-alpha-Dihydroprogesterone; D013739:Testosterone; D011374:Progesterone; D014212:Tretinoin; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D013755:Tetradecanoylphorbol Acetate