Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

Abstract

Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortisone greatly enhanced the survival of glial cells in culture. (2) The development of galactocerebroside-positive cells and the specific activity of 2′,3′-cyclic-nucleotide 3′-phosphodiesterase were stimulated by 50 nM hydrocortisone, whereas these effects were partly reversed at higher concentrations of the hormone. (3) The specific activity of glycerol-3-phosphate dehydrogenase was markedly stimulated by hydrocortisone; 1 μM or higher concentrations of hydrocortisone were required for an optimal effect. (4) The consumption of glucose and the production of lactate were lowered by hydrocortisone whereas the oxidation of [6-14C]glucose to 14CO2 was not affected. (5) Incorporation of [35S]sulfate into sulfolipids was greatly enhanced by hydrocortisone and [14C]incorporation from [1-14C]acetate into cholesterol and fatty acids was also stimulated but to a smaller extent. These results show that hydrocortisone (i) exerts a general trophic function on glial cells in our culture system; (ii) enhances the ratio of oligodendrocytes over astrocytes, possibly by directing bipotential progenitor cells to develop into oligodendrocytes; (iii) specifically induces glycerol-3-phosphate dehydrogenase in oligodendrocytes.