DEHYDROEPIANDROSTERONE-SULFATE (DHEAS) - IDENTIFICATION OF A CARRIER PROTEIN IN HUMAN LIVER AND BRAIN

Dehydroepiandrosterone sulfate (DHEAS) is the major circulating steroi d in man. Pharmacologically, it erects marked neuropsychiatric effects . Since no target receptor has been identified, me investigated whethe r the organic anion transporting polypeptide (OATP), a multispecific s teroid carrier, transports DHEAS. Expression of the human liver OATP i n Xenopus laevis oocytes resulted in high-affinity, partially Na+-depe ndent uptake of [H-3]DHEAS (K-m: 6.6 mu mol/l). DHEAS transport was in hibited by bromosulfophthalein, bile acids, sulfated estrogens and dex amethasone. Northern blot analysis showed widespread expression of OAT P in human brain. These data identify OATP as the first known target p rotein of DHEAS in human liver and brain. (C) 1998 Federation of Europ ean Biochemical Societies.