Dehydroepiandrosterone and related steroids induce multilamellar lipid structures in cultured human endothelial cells

Abstract

Pharmacologic doses of dehydroepiandrosterone (DHEA), a steroid hormone produced naturally by the adrenal cortex, may lower plasma lipoprotein levels in humans and reduce the severity of experimental atherosclerosis in rabbits. Effects of DHEA on cells of the vascular wall, particularly endothelial cells (EC), which are in direct contact with the plasma, have not been documented. The authors have found that micromolar doses of DHEA induce a consistent and reversible morphologic change in cultured EC derived from the human umbilical vein. During 24 hours of exposure to DHEA, cultured EC became loaded with phase-dense, perinuclear cytoplasmic granules, which persisted while DHEA remained in the culture medium. Certain steroids related to DHEA, particularly 17-ketosteroids, also induced perinuclear cytoplasmic granules. The granules lost their phase-density after fixed monolayers were extracted using ethanol or methanol. The granules did not form in media made with lipoprotein-deficient serum, suggesting that serum lipoproteins were involved in formation of the granules. Ultrastructurally, the granules were identical to multilamellar lipid structures, a type of pleomorphic lipid-containing lysosome found in foam cells. The granules were identified as lysosomes by positive reaction for acid phosphatase. The mechanism by which DHEA induces formation of lysosomal lipid structures remains to be determined.