STUDIES OF THE NEURONAL TRANSDIFFERENTIATION PROCESS IN CULTURED HUMAN PHEOCHROMOCYTOMA CELLS - EFFECTS OF STEROIDS WITH DIFFERING FUNCTIONAL-GROUPS ON CATECHOLAMINE CONTENT AND CELL MORPHOLOGY

The neuronal differentiation of adrenal pheochromocytoma cells from hu man subjects was studied in vitro for periods of up to 65 days. Change s with time in culture were observed in both intracellular catecholami ne content (progressive decreases in epinephrine, norepinephrine, and dopamine, except for a possible transient early increase in the latter ) and in morphology (increases in neurite outgrowth) of cells cultured in control medium; supplementation of cultures with nerve growth fact or resulted in a substantial increase in neurite formation. The effect s on these changes of the presence in the culture medium of various st eroids were Examined. The addition of 11-oxygenated steroids (aldoster one, corticosterone, cortisol, or dexamethasone) at 10(-5) M concentra tions caused at least 2.5-fold increases in mean intracellular dopamin e and norepinephrine levels; with dexamethasone, 9-10-fold increases w ere observed. Intracellular epinephrine content was also enhanced by 1 1,17-oxygenated steroids (dexamethasone and cortisol), brit not by the other 11-oxygenated compounds studied. These two 11,17-oxygenated glu cocorticoids also inhibited the morphologic changes seen with extended periods in culture, decreasing the outgrowth of neurite projections a nd causing cells to attain a vacuolated and granular appearance; the p resence of dexamethasone strongly inhibited the morphologic changes in duced by nerve growth factor. 11-Deoxy steroid intermediates (pregneno lone, 11-deoxycorticosterone, and 11-deoxycortisol) had little or no e ffect on catecholamine content or on morphology. Preliminary observati ons suggest that C-18 and C-19 sex steroid hormones (17 beta-estradiol and testosterone) may have morphologic effects opposite to those of t he 11-oxygenated compounds, showing a slight stimulator? influence on the formation of neurite projections, but no significant effect on cat echolamine content. (Steroids 63:587-594, 1998) (C) 1998 by Elsevier S cience Inc.