title: High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C.
abstract: 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.
authors.affiliation: Departments of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: a.e.bochem@amc.uva.nl.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Bochem
authors.affiliation: Departments of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.affiliation: Departments of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands.
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.affiliation: Departments of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.affiliation: Departments of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mahdi M
authors.initials: MM
authors.lastname: Motazacker
authors.affiliation: Departments of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Department of Pathology and Medical Biology, Department of Molecular Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kuivenhoven
authors.affiliation: Departments of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik S G
authors.initials: ESG
authors.lastname: Stroes
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000652:urine; D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis* / Q000652:urine
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: cortisol; dyslipidemia; high density lipoprotein cholesterol; hypoalphalipoproteinemia; steroid hormones