API

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Relationship: 2582

Title

A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Increased, Steroidogenic acute regulatory protein (StAR) leads to Increased, estrogens

Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER). More help
Increased, Steroidogenic acute regulatory protein (StAR)
Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER). More help
Increased, estrogens

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name Adjacency Weight of Evidence Quantitative Understanding Point of Contact Author Status OECD Status
Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia adjacent High Moderate Cataia Ives (send email) Under development: Not open for comment. Do not cite Under Development

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 KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER.  More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
rat Rattus norvegicus Low NCBI
mice Mus sp. Low NCBI
fish fish Low NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help
Sex Evidence
Female High
Male Low

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER.  More help
Term Evidence
Adult, reproductively mature High

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

Steroidogenic acute regulatory (StAR) protein (37-kDa) is synthesized with a mitochondrial leader sequence in response to the cell stimulation to produce steroid and plays a crucial role in steroidogenesis (Hanukoglu, 1992).  Research had shown in human ovary StAR protein was produced in response to the Luteinizing Hormone (LH) surge (Kiriakidou et al., 1996). In particular, StAR protein involved in the transportation of the cholesterol (substrate for steroid hormone) from outer to inner mitochondrial membrane. This step is crucial and rate limiting in steroid biosynthesis. In the inner membrane of the mitochondria with the help of cleaved cholesterol pregnenolone is formed, which is the precursor to the different steroid hormones including estrogen (P. R. Manna et al., 2016). Effects of StAR protein on steroidal biosynthesis had been studied by number of researchers (Pulak R Manna et al., 2002; Pescador et al., 1996; Stocco, 2001).

Estradiol synthesis during menstrual cycle is governed via expression of StAR protein synthesis. Presence of StAR protein allows follicular production of androgens which allows the progesterone dominated microenvironment and help in sexual differentiation, growth, reproduction, development and metabolism. Kusakabe et al., had shown in trout fish (Salvelinus fontinalis) model that peak of StAR protein coincide with the menstrual hormone production peak (Kusakabe et al., 2002). Research had shown some toxic chemicals can caused alteration in steroidal regulation and resulted in the agonist effect on estrogen receptors (Lauretta et al., 2019).

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings.  Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

Evidence Map 2.0

ID Experimental Design Species Upstream Observation Downstream Observation Citation (first author, year) Notes

Evidence Map

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help
Title First Author
Biological Plausibility
Dose Concordance
Temporal Concordance
Incidence Concordance
Biological Plausibility
Dose Concordance Evidence
Temporal Concordance Evidence
Incidence Concordance Evidence
Uncertainties and Inconsistencies
Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

Chang et al., had investigated the effects of antimullerian hormone (AMH) on estradiol production in primary culture of human granulosa-lutein (hGL) cells. In the control cell estradiol concentration was found 43.2–93.7 ng/mL. Whereas,treatment with AMH (10 ng/mL) significantly reduced the estradiol accumulation in the cells (Chang et al., 2013).

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references.  More help

Arukwe had shown nonylphenol (15 µg/L) can induce the StAR protein in juvenile Atlantic salmon (Salmo salar) fish (Arukwe, 2005).

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

Adult