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Event: 266

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decrease, Steroidogenic acute regulatory protein (STAR)

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
steroid hormone secreting cell

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
gene expression	STAR	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
PPARα activation leading to impaired fertility	KeyEvent	Arthur Author (send email)	Open for citation & comment	Under Review

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
mouse	Mus musculus	Moderate	NCBI
human	Homo sapiens	Moderate	NCBI
rat	Rattus norvegicus	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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].

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

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

References

List of the literature that was cited for this KE description. More help

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.