Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines

Jon Hennebold, Raymond A. Daynes

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Metabolism of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA) occurs within specific anatomical compartments in vivo through the actions of the enzyme DHEAS sulfatase. This enzymatic activity facilitates the conversion of hydrophilic DHEAS to the hydrophobic species DHEA, which can then be further metabolized to other steroid hormones. High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function. Therefore, control over the activity of DHEAS sulfatase may represent an important regulatory process for the production of DHEA and its metabolites. Homogenous populations of macrophages from normal mice were found to effectively convert DHEAS to DHEA in vitro. DHEAS sulfatase activity could be markedly depressed after exposure of these cells to a variety of nonspecific macrophage activators [i.e. zymosan, polyinosine/cytosine, heat- killed bacteria, or bacterial lipopolysaccharide (LPS)]. Inhibition of DHEAS metabolism was found to require protein synthesis, because temporary abrogation of protein synthesis with cycloheximide eliminated the ability of LPS to depress the conversion of DHEAS to DHEA. Additionally, exposure of LPS-nonresponsive macrophages to supernatants derived from LPS-treated BALB/c macrophages inhibited their ability to convert DHEAS to DHEA. Potent inhibition of sulfatase activity could be achieved by directly exposing murine macrophages to interferon-α (IFNα), IFNβ, or tumor necrosis factor- α, but not interleukin-1, interleukin-6, granulocyte-macrophage colony- stimulating factor, transforming growth factor-β, platelet-derived growth factor, or the T-cell product IFNγ. Our results indicate that macrophage metabolism of DHEAS to DHEA is down-regulated after cellular activation. Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-α and IFNα/β.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalEndocrinology
Volume135
Issue number1
DOIs
StatePublished - Jul 1994
Externally publishedYes

Fingerprint

Dehydroepiandrosterone Sulfate
Dehydroepiandrosterone
Steryl-Sulfatase
Macrophages
Cytokines
Interferons
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Sulfatases
Zymosan
Cytosine
Platelet-Derived Growth Factor
Transforming Growth Factors
Cycloheximide
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Interleukin-6
Proteins
Hot Temperature
Steroids

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines. / Hennebold, Jon; Daynes, Raymond A.

In: Endocrinology, Vol. 135, No. 1, 07.1994, p. 67-75.

Research output: Contribution to journalArticle

@article{52310075c83944feb6df2f5666ab420d,
title = "Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines",
abstract = "Metabolism of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA) occurs within specific anatomical compartments in vivo through the actions of the enzyme DHEAS sulfatase. This enzymatic activity facilitates the conversion of hydrophilic DHEAS to the hydrophobic species DHEA, which can then be further metabolized to other steroid hormones. High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function. Therefore, control over the activity of DHEAS sulfatase may represent an important regulatory process for the production of DHEA and its metabolites. Homogenous populations of macrophages from normal mice were found to effectively convert DHEAS to DHEA in vitro. DHEAS sulfatase activity could be markedly depressed after exposure of these cells to a variety of nonspecific macrophage activators [i.e. zymosan, polyinosine/cytosine, heat- killed bacteria, or bacterial lipopolysaccharide (LPS)]. Inhibition of DHEAS metabolism was found to require protein synthesis, because temporary abrogation of protein synthesis with cycloheximide eliminated the ability of LPS to depress the conversion of DHEAS to DHEA. Additionally, exposure of LPS-nonresponsive macrophages to supernatants derived from LPS-treated BALB/c macrophages inhibited their ability to convert DHEAS to DHEA. Potent inhibition of sulfatase activity could be achieved by directly exposing murine macrophages to interferon-α (IFNα), IFNβ, or tumor necrosis factor- α, but not interleukin-1, interleukin-6, granulocyte-macrophage colony- stimulating factor, transforming growth factor-β, platelet-derived growth factor, or the T-cell product IFNγ. Our results indicate that macrophage metabolism of DHEAS to DHEA is down-regulated after cellular activation. Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-α and IFNα/β.",
author = "Jon Hennebold and Daynes, {Raymond A.}",
year = "1994",
month = "7",
doi = "10.1210/en.135.1.67",
language = "English (US)",
volume = "135",
pages = "67--75",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines

AU - Hennebold, Jon

AU - Daynes, Raymond A.

PY - 1994/7

Y1 - 1994/7

N2 - Metabolism of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA) occurs within specific anatomical compartments in vivo through the actions of the enzyme DHEAS sulfatase. This enzymatic activity facilitates the conversion of hydrophilic DHEAS to the hydrophobic species DHEA, which can then be further metabolized to other steroid hormones. High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function. Therefore, control over the activity of DHEAS sulfatase may represent an important regulatory process for the production of DHEA and its metabolites. Homogenous populations of macrophages from normal mice were found to effectively convert DHEAS to DHEA in vitro. DHEAS sulfatase activity could be markedly depressed after exposure of these cells to a variety of nonspecific macrophage activators [i.e. zymosan, polyinosine/cytosine, heat- killed bacteria, or bacterial lipopolysaccharide (LPS)]. Inhibition of DHEAS metabolism was found to require protein synthesis, because temporary abrogation of protein synthesis with cycloheximide eliminated the ability of LPS to depress the conversion of DHEAS to DHEA. Additionally, exposure of LPS-nonresponsive macrophages to supernatants derived from LPS-treated BALB/c macrophages inhibited their ability to convert DHEAS to DHEA. Potent inhibition of sulfatase activity could be achieved by directly exposing murine macrophages to interferon-α (IFNα), IFNβ, or tumor necrosis factor- α, but not interleukin-1, interleukin-6, granulocyte-macrophage colony- stimulating factor, transforming growth factor-β, platelet-derived growth factor, or the T-cell product IFNγ. Our results indicate that macrophage metabolism of DHEAS to DHEA is down-regulated after cellular activation. Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-α and IFNα/β.

AB - Metabolism of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA) occurs within specific anatomical compartments in vivo through the actions of the enzyme DHEAS sulfatase. This enzymatic activity facilitates the conversion of hydrophilic DHEAS to the hydrophobic species DHEA, which can then be further metabolized to other steroid hormones. High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function. Therefore, control over the activity of DHEAS sulfatase may represent an important regulatory process for the production of DHEA and its metabolites. Homogenous populations of macrophages from normal mice were found to effectively convert DHEAS to DHEA in vitro. DHEAS sulfatase activity could be markedly depressed after exposure of these cells to a variety of nonspecific macrophage activators [i.e. zymosan, polyinosine/cytosine, heat- killed bacteria, or bacterial lipopolysaccharide (LPS)]. Inhibition of DHEAS metabolism was found to require protein synthesis, because temporary abrogation of protein synthesis with cycloheximide eliminated the ability of LPS to depress the conversion of DHEAS to DHEA. Additionally, exposure of LPS-nonresponsive macrophages to supernatants derived from LPS-treated BALB/c macrophages inhibited their ability to convert DHEAS to DHEA. Potent inhibition of sulfatase activity could be achieved by directly exposing murine macrophages to interferon-α (IFNα), IFNβ, or tumor necrosis factor- α, but not interleukin-1, interleukin-6, granulocyte-macrophage colony- stimulating factor, transforming growth factor-β, platelet-derived growth factor, or the T-cell product IFNγ. Our results indicate that macrophage metabolism of DHEAS to DHEA is down-regulated after cellular activation. Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-α and IFNα/β.

UR - http://www.scopus.com/inward/record.url?scp=0028302689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028302689&partnerID=8YFLogxK

U2 - 10.1210/en.135.1.67

DO - 10.1210/en.135.1.67

M3 - Article

VL - 135

SP - 67

EP - 75

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 1

ER -