Event:266

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Event Title

Steroidogenic acute regulatory protein (STAR), Decrease
Short name: Steroidogenic acute regulatory protein (STAR), Decrease

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
PPARα activation in utero leading to impaired fertility in males KE Weak

Taxonomic Applicability

Name Scientific Name Evidence Links
mouse Mus musculus Moderate NCBI
human Homo sapiens Moderate NCBI
rat Rattus sp. Strong NCBI

Level of Biological Organization

Biological Organization
Cellular

How this Key Event works

Biological state

Steroidogenic acute regulatory protein (StAR) functions as a cholesterol transfer protein and acts directly on lipids of the outer mitochondrial membrane to promote cholesterol translocation (Stocco 2001). Reduction of the protein impacts on the amount of substrate available for steroidogenesis.


Biological compartments

StAR is expressed principally in steroidogenic tissues (Bauer et al. 2000).

General role in biology

StAR is required for cholesterol shuttling across the mitochondrial membrane and appears to regulate acute steroid production (Clark and Stocco, 1997). Transcriptional or translational inhibition of StAR expression results in a dramatic decrease in steroid biosynthesis, whereas ~10–15% of steroid synthesis appears to be mediated through StAR-independent mechanisms (Manna et al. 2001) (Clark and Stocco, 1997). In contrast, chronically regulated steroid production appears to be largely mediated by increased transcription of steroidogenic enzymes (Hum and Miller 1993).

How it is Measured or Detected

The StAR expression can be measured by RT-PCR (mRNA) and on the protein level (western blot). The StAR expression as well as other steroidogenic proteins can be measured in vitro cultured Leydig cells. The methods for culturing Leydig cells can be found in the Database Service on Alternative Methods to animal experimentation (DB-ALM): Leydig Cell-enriched Cultures [1] Testicular Organ and Tissue Culture Systems [2].

Evidence Supporting Taxonomic Applicability

StAR has been cloned from many species, and is highly conserved among mammals, birds, amphibians and fish (Bauer et al. 2000).

References

Bauer, M P, J T Bridgham, D M Langenau, A L Johnson, and F W Goetz. 2000. “Conservation of Steroidogenic Acute Regulatory (StAR) Protein Structure and Expression in Vertebrates.” Molecular and Cellular Endocrinology 168 (1-2) (October 25): 119–25.

Hum, D W, and W L Miller. 1993. “Transcriptional Regulation of Human Genes for Steroidogenic Enzymes.” Clinical Chemistry 39 (2) (February): 333–40.

Manna, P R, J Kero, M Tena-Sempere, P Pakarinen, D M Stocco, and I T Huhtaniemi. 2001. “Assessment of Mechanisms of Thyroid Hormone Action in Mouse Leydig Cells: Regulation of the Steroidogenic Acute Regulatory Protein, Steroidogenesis, and Luteinizing Hormone Receptor Function.” Endocrinology 142 (1) (January): 319–31. doi:10.1210/endo.142.1.7900.

Stocco, D M. 2001. “StAR Protein and the Regulation of Steroid Hormone Biosynthesis.” Annual Review of Physiology 63 (January): 193–213. doi:10.1146/annurev.physiol.63.1.193.