High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C
Open accessAbstract
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.
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The adrenal glands obtain cholesterol from HDL and LDL to synthesize steroid hormones and neuroactive steroids.
“The adrenal glands obtain cholesterol from HDL and LDL to synthesize steroid hormones and neuroactive steroids [9, 10].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [9]
The paper’s introductory passages say adrenal steroid-hormone synthesis requires cholesterol and support HDL as a cholesterol donor. They also say LDL probably does not play a major role in delivering cholesterol for steroid-hormone production in humans. The cited passages do not address neuroactive-steroid synthesis, so the full claim is not supported. (LLM, conf=0.88)
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References 34 · Cited by 56
- Authors
- Bochem, A. E., Holleboom, A. G., Romijn, J. A., Hoekstra, M., Dallinga-Thie, G. M., Motazacker, M. M., Hovingh, G. K., Kuivenhoven, J. A., & Stroes, E. S. G.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- University Medical Center Groningen (NL)
- Corresponding author
- Bochem, Andrea E.
- ORCID
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 54
- Issue
- 6
- Pages
- 1698-1704
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3646470
- OpenAlex
- W2165275486
- Cited by
- 56
- References
- 34
- Citations by year
- 2025: 5 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 7 · 2015: 5 · 2014: 6
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- high-density lipoprotein, adrenal steroidogenesis, low HDL cholesterol, ABCA1 mutations, urinary 17-ketosteroids, ACTH stimulation test
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Adult, Aged, Humans, Phosphatidylcholine-Sterol O-Acyltransferase, Cholesterol, HDL, Male, Middle Aged, Steroids, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter 1
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