High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C

• Published in: Journal of lipid research Vol. 54; no. 6; pp. 1698 - 1704
• Main Authors: Bochem, Andrea E., Holleboom, Adriaan G., Romijn, Johannes A., Hoekstra, Menno, Dallinga-Thie, Geesje M., Motazacker, Mahdi M., Hovingh, G.Kees, Kuivenhoven, Jan A., Stroes, Erik S.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2013; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Adrenal Glands - metabolism; Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - urine; Adult; Aged; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Cholesterol, HDL - blood; Cholesterol, HDL - urine; cortisol; dyslipidemia; high density lipoprotein cholesterol; Humans; hypoalphalipoproteinemia; Male; Middle Aged; Patient-Oriented and Epidemiological Research; Phosphatidylcholine-Sterol O-Acyltransferase - genetics; Phosphatidylcholine-Sterol O-Acyltransferase - metabolism; steroid hormones; Steroids - biosynthesis; Steroids - urine; cortisol; steroid hormones; dyslipidemia; high density lipoprotein cholesterol; hypoalphalipoproteinemia
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.P033449

Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To study this, steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP binding cassette transporter A1 (ABCA1) (n = 24), lecithin:cholesterol acyltransferase (LCAT) (n = 40), as well as in 11 subjects with low HDL cholesterol (HDL-C) without ABCA1/LCAT mutations. HDL-C levels were 39% lower in the ABCA1, LCAT, and low HDL-C groups compared with controls (all P < 0.001). In all groups with low HDL-C levels, urinary excretion of 17-ketogenic steroids was reduced by 33%, 27%, and 32% compared with controls (all P < 0.04). In seven carriers of either type of mutation, adrenocorticotropic hormone (ACTH) stimulation did not reveal differences from normolipidemic controls. In conclusion, this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL-C, irrespective of its molecular origin. These findings lend support to a role for HDL as a cholesterol donor for basal adrenal steroidogenesis in humans.