Evidence for a potential role for HDL as an important source of cholesterol in human adrenocortical tumors via the CLA-1 pathway

CLA-1, a human homologue of rodent scavenger receptor class B1 (SR-B1), has been identified as a receptor for high density lipoprotein (HDL) and is hi ghly expressed in the adrenal gland. Several studies have indicated that HD L might be a source of cholesterol for steroidogenesis in the adrenal gland . In this study, we show that ACTH and its second messenger cAMP stimulated GLA-1 protein expression in a human adrenocortical cell line. We also dete rmined whether CLA-1 plays an important role in steroidogenesis by investig ating GLA-1 expression levels in various adrenal tumors including the adeno mas of Gushing's and Conn's syndrome. Western blot analysis showed that CLA -1 expression was much higher in the tumors of Gushing's syndrome than in n on-tumor lesions of Conn's syndrome and pheochromocytoma. We were able to d etect a strong CLA-1 signal in tumors of Conn's syndrome, too. On the other hand, much less CLA-I expression was detected in Gushing's adenoma adjacen t adrenal glands. The immunohistochemical analysis showed that CLA-1 was ex pressed in the outer region of the adrenal cortex mainly in plasma membrane s of the cortical cells but not in the medulla. These findings demonstrated for the first time that ACTH increased CLA-1 protein in cultured human adr enocortical cells, and that cortisol- and aldosterone-secreting adenomas ha d high CLA-1 proteins in their cell surfaces.