INHIBITION OF MIGRATION AND PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS BY DEHYDROEPIANDROSTERONE-SULFATE

Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) an the most abu ndant steroids in humans, and their serum concentrations progressively decrease with age. Although relationships between DHEA(-S) and many a ge-related illnesses have been postulated, the mechanisms for their ef fects remain unknown, and specific receptors for these molecules have not been identified. In this paper, to investigate the role of DHEA(-S ) in atherogenesis, we studied the proliferation and migration of a ra bbit vascular smooth muscle cell line, SM-3, in the presence of DHEA(- S). Cellular proliferation was inhibited by DHEA-S, and to a lesser ex tent by DHEA. Modified Boyden's chamber assays revealed that DHEA-S in hibited the migration of SM-3 cells toward PDGF-BB. In cell attachment assays, DHEA-S inhibited the attachment of SM3 cells to fibronectin. It was suggested that the inhibitory effect of DHEA-S for SM-3 prolife ration and migration was due to the decreased interaction with fibrone ctin. Scatchard analysis revealed the presence of two populations of D HEA-S binding sites in the nuclear fraction, and a smaller number in t he cytosolic fraction. Since the dissociation constant of the higher a ffinity site was similar to the serum DHEA-S concentration in humans ( K-d = 5.8 mu M), this binding site could be functional under physiolog ic conditions. These findings suggest that there may be receptor-media ted anti-atherogenic actions of DHEA-S. (C) 1998 Elsevier Science B.V.