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 highly expressed in the adrenal gland. Several studies have indicated that HDL 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 CLA-1 protein expression in a human adrenocortical cell line. We also determined whether CLA-1 plays an important role in steroidogenesis by investigating CLA-1 expression levels in various adrenal tumors including the adenomas of Cushing's and Conn's syndrome. Western blot analysis showed that CLA-1 expression was much higher in the tumors of Cushing's syndrome than in non-tumor lesions of Conn's syndrome and pheochromocytoma. We were able to detect a strong CLA-1 signal in tumors of Conn's syndrome, too. On the other hand, much less CLA-1 expression was detected in Cushing's adenoma adjacent adrenal glands. The immunohistochemical analysis showed that CLA-1 was expressed in the outer region of the adrenal cortex mainly in plasma membranes 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 adrenocortical cells, and that cortisol- and aldosterone-secreting adenomas had high CLA-1 proteins in their cell surfaces.