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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context: Adrenal 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 b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3α-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 andCYB5Ain 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.

Original languageEnglish (US)
Pages (from-to)4585-4593
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Androstenediol
Cytochromes b5
Dehydroepiandrosterone Sulfate
Sulfates
Zona Reticularis
Steroids
Serum
Steroid 17-alpha-Hydroxylase
Dehydroepiandrosterone
Fluorescent Antibody Technique
3-Hydroxysteroid Dehydrogenases
Zona Fasciculata
Liquid chromatography
Small Interfering RNA
Adrenal Glands
Tandem Mass Spectrometry
Mass spectrometry
Liquid Chromatography
Phenotype

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Rege, J., Karashima, S., Lerario, A. M., Smith, J. M., Auchus, R. J., Kasa-Vubu, J. Z., ... Rainey, W. E. (2016). Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate. Journal of Clinical Endocrinology and Metabolism, 101(12), 4585-4593. https://doi.org/10.1210/jc.2016-2864

Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate. / Rege, Juilee; Karashima, Shigehiro; Lerario, Antonio M.; Smith, Joshua M.; Auchus, Richard J.; Kasa-Vubu, Josephine Z.; Sasano, Hironobu; Nakamura, Yasuhiro; White, Perrin C.; Rainey, William E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 12, 01.12.2016, p. 4585-4593.

Research output: Contribution to journalArticle

Rege, J, Karashima, S, Lerario, AM, Smith, JM, Auchus, RJ, Kasa-Vubu, JZ, Sasano, H, Nakamura, Y, White, PC & Rainey, WE 2016, 'Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 12, pp. 4585-4593. https://doi.org/10.1210/jc.2016-2864
Rege, Juilee ; Karashima, Shigehiro ; Lerario, Antonio M. ; Smith, Joshua M. ; Auchus, Richard J. ; Kasa-Vubu, Josephine Z. ; Sasano, Hironobu ; Nakamura, Yasuhiro ; White, Perrin C. ; Rainey, William E. / Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 12. pp. 4585-4593.
@article{37332b0684a34e33a22ef0e2a3a47873,
title = "Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate",
abstract = "Context: Adrenal 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 b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3α-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 andCYB5Ain 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.",
author = "Juilee Rege and Shigehiro Karashima and Lerario, {Antonio M.} and Smith, {Joshua M.} and Auchus, {Richard J.} and Kasa-Vubu, {Josephine Z.} and Hironobu Sasano and Yasuhiro Nakamura and White, {Perrin C.} and Rainey, {William E.}",
year = "2016",
month = "12",
day = "1",
doi = "10.1210/jc.2016-2864",
language = "English (US)",
volume = "101",
pages = "4585--4593",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate

AU - Rege, Juilee

AU - Karashima, Shigehiro

AU - Lerario, Antonio M.

AU - Smith, Joshua M.

AU - Auchus, Richard J.

AU - Kasa-Vubu, Josephine Z.

AU - Sasano, Hironobu

AU - Nakamura, Yasuhiro

AU - White, Perrin C.

AU - Rainey, William E.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Context: Adrenal 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 b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3α-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 andCYB5Ain 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.

AB - Context: Adrenal 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 b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3α-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 andCYB5Ain 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.

UR - http://www.scopus.com/inward/record.url?scp=85003634498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85003634498&partnerID=8YFLogxK

U2 - 10.1210/jc.2016-2864

DO - 10.1210/jc.2016-2864

M3 - Article

VL - 101

SP - 4585

EP - 4593

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -