Regulation of adrenal scavenger receptor-BI expression by ACTH and cellular cholesterol pools

J Lipid Res. 1999 Oct;40(10):1799-805.

Abstract

Scavenger receptor BI (SR-BI) mediates selective uptake of high density lipoprotein (HDL) cholesteryl ester in the liver and adrenal gland. Adrenal SR-BI is increased both in adrenocorticotropic hormone (ACTH)-treated mice and also in apolipoprotein A-I knock-out (apoA-I0) mice which have depleted adrenal cholesterol stores. The goal of the present study was to determine whether adrenal cholesterol stores and ACTH have independent effects on SR-BI expression in adrenal gland. Adrenal SR-BI levels were 5-fold higher in apoA-I0 than wild-type mice when killed under low stress condition, and plasma ACTH levels were similar in both strains. After male apoA-I0 or wild-type mice were treated with dexamethasone to suppress ACTH release, adrenal SR-BI protein levels were decreased in both groups but remained 13-fold higher in apoA-I0 than in wild-type mice. By contrast, uncontrolled stress or supplemental ACTH treatment increased SR-BI levels but narrowed the difference in SR-BI expression between apoA-I0 and wild-type. Cholesterol depletion by beta-cyclodextrin in cultured Y1-BS1 adrenal cells also led to a rapid 2- to 3-fold increase in SR-BI mRNA and protein levels, in association with a significant depletion of cellular free cholesterol. These results indicate that depletion of adrenal cholesterol stores can act independently from ACTH to increase SR-BI expression, but in vivo this effect is diminished under high ACTH conditions. Both stimuli may increase selective uptake via increased SR-BI as a means of replenishing cholesterol stores for steroid hormone synthesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism*
  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / pharmacology
  • Adrenocorticotropic Hormone / physiology*
  • Animals
  • Apolipoprotein A-I / deficiency
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / physiology
  • CD36 Antigens / genetics*
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Cyclodextrins
  • Dexamethasone / pharmacology
  • Female
  • Gene Expression Regulation* / drug effects
  • Indicators and Reagents
  • Kinetics
  • Male
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic*
  • Receptors, Lipoprotein / genetics
  • Receptors, Scavenger
  • Scavenger Receptors, Class B

Substances

  • Apolipoprotein A-I
  • CD36 Antigens
  • Cyclodextrins
  • Indicators and Reagents
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Cholesterol