Role of apolipoprotein A-I in the anabolic effect of steroid hormones

As early shown, a portion of steroid hormones binds to blood lipoproteins, primarily to high-density lipoproteins (HDL) [Panin et al. 1988]. Steroid hormones together with HDL are captured by resident macrophages of the liver where in secondary lysosomes HDL are degraded to form apoA-I and steroid hormones restore a ∆4, 3-keto group with the participation of 5-α and 5β- reductases to give rise to tetrahydro compounds. In this study, an attempt was undertaken to show a role of a complex of some steroid hormones with apo A-I in realization of the anabolic action of these steroid hormones by using the cultured hepatocytes and concurrently cultured hepatocytes and Kupffer’s cells isolated from the liver of male Wistar rats weighing 180-200 g. Steroid hormones having an anabolic action, such as androsterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and tetrahydrocortisol as ingredients of a complex with apolipoprotein A-I (apoA-I), increased the rate of protein biosynthesis and dehydroepiandrosterone sulfate and tetrahydrocortisol also did the rate of DNA synthesis in the cultured hepatocytes. All the hormones had a restored ∆4,3-keto group in the A ring structure. Restoration of this group of steroid hormones and formation of their complex with apoA-I are associated with the action of resident macrophages (Kupffer’s cells). That is the reason that addition of HDL (a source of apoA-I) and cortisol (a source of the restored form - tetrahydrocortisol) to the coculture of hepatocytes and macrophages, by concurrently stimulating the latter by lipopolysaccharide led to a significant increase in the rate of protein and DNA biosynthesis. The findings show an important role of a ∆4,3-keto group of the A ring of steroid hormones and their complex with apo A-I in realizing the anabolic action of steroids.