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A constant supply of cholesterol is needed as a substrate for steroid hormone synthesis in steroidogenic tissues. Although there are three potential sources, which could contribute to the 'cholesterol pool', needed for steroidogenesis (i.e., de novo synthesis, hydrolysis of stored cholesteryl esters and exogenous lipoproteins), current evidence suggests that plasma lipoproteins are the major source of cholesterol for steroid production in adrenal gland, ovary and, under certain conditions, testicular Leydig cells. In many species, steroid producing cells and tissues obtain this lipoprotein-cholesterol by a unique pathway in which circulating lipoproteins bind to the surface of the steroidogenic cells and contribute their cholesteryl esters to the cells by a 'selective' process. This is a process in which cholesterol is selectively absorbed while the lipoprotein remains at the cell surface. The discovery of a specific receptor for this process (scavenger receptor class B, type I, known as SR-BI) has revolutionized our knowledge about the selective uptake pathway. The present review summarizes the functional importance of the selective pathway as a bulk cholesterol delivery system for steroidogenesis, and attempts to detail the expression, regulation and characteristics of SR-BI as it is deployed in steroidogenic systems as a means of achieving cholesterol balance.

The steroidogenic tissues have a special requirement for cholesterol, which is used as a substrate for steroid hormone biosynthesis. In many species this cholesterol is obtained from plasma lipoproteins by a unique pathway in which circulating lipoproteins bind to the surface of the steroidogenic cells and contribute their cholesteryl esters to the cells by a 'selective' process in which the whole lipoprotein particle does not enter the cell. This review describes the lipoprotein selective cholesteryl ester uptake process and its specific partnership with the HDL receptor, scavenger receptor class BI (SR-BI). It describes the characteristics of the selective pathway, and the molecular properties, localization, regulation, anchoring sites and potential mechanisms of action of SR-BI in facilitating cholesteryl ester uptake by steroidogenic cells.

This study examined the in vivo relationship between expression of the HDL receptor scavenger receptor class B (SR-BI) and corresponding structural changes in the rat adrenocortical cell microvillar compartment. Using hormonal stimulation and withdrawal protocols, we were able to manipulate adrenal SR-BI levels and carry out qualitative and quantitative measurements correlating SR-BI expression with microvillar mass and microvillar channel formation. Young male rats were used as controls or treated with adrenocorticotropin hormone (ACTH) (24 h), 17alpha-ethinyl estradiol (17alpha-E2) (5 days), or dexamethasone (DEX) (24 h). Quantitative Western blot analysis and immunocytochemistry indicated that ACTH and 17alpha-E2 treatment greatly increased SR-BI expression in the adrenal (especially in the microvillar compartment of adrenocortical cells), whereas DEX treatment led to a decrease of SR-BI by all measurements. At the same time, striking ultrastructural changes occurred in the adrenocortical cell microvillar compartment: e.g., microvillar area and microvillar channel formation and complexity dramatically increased (compared with control values) after ACTH or 17alpha-E2 treatment, whereas the same values declined after DEX treatment. These measurements illustrate the exceptional flexibility and responsiveness of the microvillar compartment to hormonal stimuli, and suggest that regulation of SR-BI expression and structural configuration of the surface of steroidogenic cells goes hand in hand.