Cholesterol sulfate

A naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation

J. David Lambeth, Xiangxi Xu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.

Original languageEnglish
Pages (from-to)85-99
Number of pages15
JournalEndocrine Research
Volume15
Issue number1-2
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Anticholesteremic Agents
Cholesterol
Pregnenolone
Mitochondria
Adrenal Cortex
Ether
Adrenocorticotropic Hormone
Cytochromes
Corticosterone
cholesteryl sulfate
Steroids
Hormones
Injections

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{635265d2f0a842e7869e7ea69d6bc660,
title = "Cholesterol sulfate: A naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation",
abstract = "Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.",
author = "Lambeth, {J. David} and Xiangxi Xu",
year = "1989",
month = "1",
day = "1",
doi = "10.1080/07435808909039090",
language = "English",
volume = "15",
pages = "85--99",
journal = "Endocrine Research",
issn = "0743-5800",
publisher = "Informa Healthcare",
number = "1-2",

}

TY - JOUR

T1 - Cholesterol sulfate

T2 - A naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation

AU - Lambeth, J. David

AU - Xu, Xiangxi

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.

AB - Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.

UR - http://www.scopus.com/inward/record.url?scp=0024354931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024354931&partnerID=8YFLogxK

U2 - 10.1080/07435808909039090

DO - 10.1080/07435808909039090

M3 - Article

VL - 15

SP - 85

EP - 99

JO - Endocrine Research

JF - Endocrine Research

SN - 0743-5800

IS - 1-2

ER -