Neurosteroid transport by the organic solute transporter OSTα-OSTβ

P>A variety of steroids, including pregnenolone sulfate (PREGS) and dehydroepiandrosterone sulfate (DHEAS) are synthesized by specific brain cells, and are then delivered to their target sites, where they exert potent effects on neuronal excitability. The present results demonstrate that [3H]DHEAS and [3H]PREGS are relatively high affinity substrates for the organic solute transporter, OST alpha-OST beta, and that the two proteins that constitute this transporter are selectively localized to steroidogenic cells in the cerebellum and hippocampus, namely the Purkinje cells and cells in the cornu ammonis region in both mouse and human brain. Analysis of Ost alpha and Ost beta mRNA levels in mouse Purkinje and hippocampal cells isolated via laser capture microdissection supported these findings. In addition, Ost alpha-deficient mice exhibited changes in serum DHEA and DHEAS levels, and in tissue distribution of administered [3H]DHEAS. OST alpha and OST beta proteins were also localized to the zona reticularis of human adrenal gland, the major region for DHEAS production in the periphery. These results demonstrate that OST alpha-OST beta is localized to steroidogenic cells of the brain and adrenal gland, and that it modulates DHEA/DHEAS homeostasis, suggesting that it may contribute to neurosteroid action.