Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate
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CONTEXT: type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. OBJECTIVE: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. PARTICIPANTS AND METHODS: Δ5-steroid sulfates were quantified by liquid chromatography-tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5-18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2-35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. RESULTS: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. CONCLUSION: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.
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Other Δ5 steroids, e.g. pregnenolone, 17α-hydroxypregnenolone and androstenediol, can also be released in their respective sulfated form.
“Other Δ5 steroids, e.g. pregnenolone, 17α-hydroxypregnenolone and androstenediol, can also be released in their respective sulfated form [[42], [43], [44]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [44]
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Adrenal venous sampling for primary aldosteronism
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Self-citationSerum and hair steroid profiles and their associations with body composition in adolescence
Liimatta, J., Huotari, J., du Toit, T., Flueck, C. E., Jääskeläinen, J., Hackney, A. C., Häkkinen, M. R., Lehtonen, M., Auriola, S. O. K., Lakka, T. A., et al. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf235
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Self-citation
- Authors
- Rege, J., Karashima, S., Lerario, A. M., Smith, J. M., Auchus, R. J., Kasa-Vubu, J. Z., Sasano, H., Nakamura, Y., White, P. C., & Rainey, W. E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Texas Southwestern Medical Center, Dallas, Texas 75235
- University of Michigan (US)
- Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Texas Southwestern Medical Center, Dallas, Texas 75235
- Tohoku University (JP)
- Tohoku Medical and Pharmaceutical University (JP)
- Corresponding author
- Rainey, William E.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-09-13
- Volume
- 101
- Issue
- 12
- Pages
- 4585-4593
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5155691
- OpenAlex
- W2520996721
- Cited by
- 40
- References
- 58
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 10 · 2017: 2
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan (48109, DK089503)
- National Institutes of Health (UL1TR000433, R01DK43140, DK089503)
- College of Pharmacy, University of Michigan
- Japan Society for the Promotion of Science (15H04711)
- National Institute of General Medical Sciences (R01GM086596)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK089503, R01DK069950, R01 DK43140, R01DK043140, P30DK089503)
- National Center for Advancing Translational Sciences
- Michigan Nutrition Obesity Research Center, Medical School, University of Michigan
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- CYB5A, DHEA sulfate, pregnenolone sulfate, 17,20-lyase activity, HSD3B2, adrenocortical cells, children
- MeSH terms
- Adolescent, Adrenal Glands, Adult, Age Factors, Child, Child, Preschool, Female, Humans, Human Development, 17-alpha-Hydroxypregnenolone, Infant, Male, Pregnenolone, Progesterone Reductase, Androstenediol, Cytochromes b5, Cell Culture Techniques, Dehydroepiandrosterone Sulfate, Young Adult
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