EFFECTS AND METABOLISM OF STEROID-HORMONES IN HUMAN NEUROBLASTOMA-CELLS

The development of the central nervous system is influenced by sex ste roids and by their metabolites. However, little information on the pos sible effects of steroid hormones on neuroblastoma cells is available. Human neuroblastoma cell lines have been used as a model of human neu roblasts in vitro to study the metabolism of steroid hormones; in addi tion, the effects of steroids and steroid antagonists on neuroblastoma cell growth have also been investigated. The results obtained show th at SH-SY5Y human neuroblastoma cells may actively metabolize testoster one and progesterone to their respective 5 alpha-reduced metabolites a nd that differentiation of neuroblastoma cells is paralleled by a sign ificant increase in expression of the type-1 5 alpha-reductase and of the formation of steroid metabolites. All these data are suggestive of a potential role of steroid Sac-reduced metabolites in the biology of neuroblastoma cells. Studies performed to analyze the role of steroid hormones on neuroblastoma cell proliferation show that progesterone a t low doses may induce minor stimulation, and at higher doses, a toxic effect on the neuroblastoma cell line SK-N-SH is seen. Moreover, the antiprogestin 17 beta-hydroxy-11 4-dimethylamino-phenyl-1)-17-(prop-1- ynyl)estra-4, 9-dien-3-one (RU486) decreases the proliferation of thes e cells in a dose-dependent manner. The effect of RU486 is not antagon ized by either progesterone or dexamethasone, a result that seems to e xclude the action of RU486 via classic intracellular steroid hormone r eceptors. (C) 1998 by Elsevier Science Inc.