Evidence map›Paper›PMID 27623070›Full record

ArticleThe Journal of clinical endocrinology and metabolism2016

Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate.

Juilee Rege, Shigehiro Karashima, Antonio M Lerario, Joshua M Smith, Richard J Auchus, Josephine Z Kasa-Vubu, Hironobu Sasano, Yasuhiro Nakamura, Perrin C White, William E Rainey

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 40 citations in OpenAlex.

  1. Trial
  2. Increases in fecal testosterone precede increases in fecal dehydroepiandrosterone in wild male mountain gorillas (Gorilla beringei beringei).Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Rapidity and Precision of Steroid Hormone Measurement.Journal of clinical medicine · 2022
    Review
  7. Review
  8. Normal and Premature Adrenarche.Endocrine reviews · 2021
    Review
  9. Article
  10. Article
  11. Update on adrenarche.Current opinion in pediatrics · 2020
    Review
  12. 11-Oxygenated androgens in health and disease.Nature reviews. Endocrinology · 2020
    Review
  13. Review
  14. Circulating 11-oxygenated androgens across species.The Journal of steroid biochemistry and molecular biology · 2019
    Article
  15. Steroid biomarkers in human adrenal disease.The Journal of steroid biochemistry and molecular biology · 2019
    Review
  16. Review
  17. Observational
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Juilee RegeDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Shigehiro KarashimaDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Antonio M LerarioDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Joshua M SmithDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Richard J AuchusDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Josephine Z Kasa-VubuDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Hironobu SasanoDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Yasuhiro NakamuraDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
Perrin C WhiteDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
William E RaineyDepartment of Molecular and Integrative Physiology (J.R., S.K., W.E.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Internal Medicine (A.M.L., R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; Division of Pediatric Endocrinology (J.M.S.), Specially for Children, Austin, Texas 78723; Department of Pediatrics (J.Z.K.-V.), University of Michigan, Ann Arbor, Michigan 48109; Department of Pathology (H.S., Y.N.), Tohoku University School of Medicine, Sendai, 980-8575 Japan; Division of Pathology, Faculty of Medicine (Y.N.), Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan; and Department of Pediatrics (P.C.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75235.
The University of Texas Southwestern Medical Center · USTohoku Medical and Pharmaceutical University · JPTohoku University · JPUniversity of Michigan–Ann Arbor · US

Funding

Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
MECHANISMS LEADING TO ADRENAL ZONATIONR01DK043140 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI William E Rainey · 1999 to 2026
$7.2M
Activation of androgen biosynthesis and drug metabolism by cytochrome b5R01GM086596 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI RICHARD J. AUCHUS · 2009 to 2026
$4.8M
Molecular Mechanisms of AdrenarcheR01DK069950 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAINEY, WILLIAM E · 2005 to 2019
$4.4M
NCATS NIH HHS UL1 TR000433NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R01 DK043140NIDDK NIH HHS R01 DK069950NIGMS NIH HHS R01 GM086596
6 · The paper itself

Abstract

contextAdrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b

objectiveThis 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

methodsΔ5-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.

resultsOf 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.

conclusionAdiol-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.

Indexed as

17-alpha-HydroxypregnenoloneAdolescentAdrenal GlandsAdultAge FactorsAndrostenediolCell Culture TechniquesChildChild, PreschoolCytochromes b5Dehydroepiandrosterone SulfateFemaleHuman DevelopmentHumansInfantMale17-alpha-Hydroxypregnenolone3 beta-hydroxysteroid dehydrogenase type IIAndrostenediolCYB5A protein, humanCytochromes b5Dehydroepiandrosterone SulfatePregnenolonepregnenolone sulfateProgesterone Reductase

Identifiers

PMID27623070
PMCPMC5155691
OpenAlexW2520996721

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.