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Related Experiment Videos

Progesterone blocks cholesterol translocation from lysosomes.

J D Butler1, J Blanchette-Mackie, E Goldin

  • 1Human Genetics Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.

The Journal of Biological Chemistry
|November 25, 1992
PubMed
Summary

Progesterone causes cholesterol buildup in fibroblast lysosomes, blocking its synthesis. This steroid-induced cholesterol accumulation is reversible in normal cells but not in Niemann-Pick C cells, offering insights into cholesterol transport.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Endocrinology

Background:

  • Lysosomes play a crucial role in cellular cholesterol homeostasis.
  • Disruptions in cholesterol metabolism are implicated in various diseases, including Niemann-Pick disease.
  • Steroid hormones can influence cellular lipid metabolism and transport.

Purpose of the Study:

  • To investigate the effects of progesterone on cholesterol accumulation in fibroblasts.
  • To explore the role of cholesteryl ester synthesis in progesterone-induced lysosomal lipidosis.
  • To examine the reversibility of steroid-induced cholesterol sequestration in lysosomes.

Main Methods:

  • Fibroblast cultures treated with low-density lipoprotein (LDL) and progesterone.
  • Filipin-cholesterol staining for microscopic examination of lysosomes.

Related Experiment Videos

  • Measurement of unesterified and esterified cholesterol levels.
  • Use of acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor (58035).
  • Experiments with Niemann-Pick C fibroblasts and other steroids.

    • Main Results:

    • Progesterone treatment led to a 2-fold increase in unesterified cholesterol in fibroblast lysosomes.
    • Progesterone significantly inhibited cholesteryl ester synthesis.
    • Inhibition of ACAT prevented lysosomal cholesterol storage.
    • Reversal of progesterone treatment restored lysosomal cholesterol levels and stimulated cholesteryl ester synthesis.
    • Progesterone removal did not reverse lysosomal cholesterol accumulation in Niemann-Pick C fibroblasts.

    Conclusions:

    • Progesterone induces a reversible lysosomal cholesterol lipidosis in normal fibroblasts by blocking esterification.
    • This model system provides a tool to study intracellular cholesterol transport, particularly its reversibility.
    • The observed effects highlight differences in cholesterol metabolism between normal and Niemann-Pick C fibroblasts.