This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 647

Key Event Title

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

Decreased, steroidogenic protein expression

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

Explore in a Third Party Tool

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
eukaryotic 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
regulation of steroid biosynthetic process		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
Decreased Adult Testosterone 1	KeyEvent	Undefined (send email)	Under Development: Contributions and Comments Welcome
Decreased COUP-TFII in Leydig cells leads to Impaired, Spermatogenesis	KeyEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite
Decreased COUP-TFII in Leydig cells leads to Hypospadias, increased	KeyEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite

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
mammals	mammals	Moderate	NCBI

Life Stages

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

Life stage	Evidence
Development	High

Sex Applicability

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

Term	Evidence
Unspecific	Moderate

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

Steroids are hormones that play important roles in reproductive development and function. Multiple synthesis pathways ensure that proper steroid levels are present during development. Efforts have been made to isolate when steroid levels are most critical for proper reproductive development in lab mammals by targeted disruption by toxicants during different periods of development (Foster and Harris 2005; Welsh 2008).

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

Steroidogenic protein expression is measured by changes in steroid levels. Protein families with known effects on regulation (ex. STAR steroidogenic acute regulatory protein (STaR)) or production of androgens (ex. Cytochrome P450 11 (CYP11); Cytochrome P450 17 (CYP17); 3β-Hydroxysteroid dehydrogenase (3 β-HSD)) are typically studied, with mRNA expression an indirect assessment of protein levels (Qin et al. 2008; van den Driesche et al. 2012; Mendoza-Villarroel et al. 2014). Steroid protein levels can be directly measured by immunoassay (including enzyme immunoassays (EIA) or enzyme-linked immunosorbent assay (ELISA)) and mass spectrometry (including gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS); Wudy et al. 2018).

Domain of Applicability

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

Life Stage: Development, beginning during organogenesis.

Sex: Applies to both males and females.

Taxonomic: Most representative studies have been done in mammals (humans, lab mice, lab rats); plausible for all vertebrates.

References

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

Foster, P.M.D. and Harris, M.W. 2005. Changes in Androgen-Mediated Reproductive Development in Male Rat Offspring Following Exposure to a Single Oral Dose of Flutamide at Different Gestational Ages. Toxicological Sciences 85: 1024–1032.

Mendoza-Villarroel, R.E., Robert, N.M., Martin, L.J., Brousseau, C., and Tremblay, J.J. 2014. The Nuclear Receptor NR2F2 Activates Star Expression and Steroidogenesis in Mouse MA-10 and MLTC-1 Leydig Cells. Biology of Reproduction 91(1) Article 26: 1-12.

Palermo, C.M., Foreman, J.E., Wikoff, D.S., and Lea, I. 2021. Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development. Current Research in Toxicology 2: 254–271.

Qin, J., Tsai, M.-J., and Tsai S.Y. 2008. Essential Roles of COUP-TFII in Leydig Cell Differentiation and Male Fertility. Public Library of Science One 3(9): e3285.

van den Driesche, S., Walker, M., McKinnel, C., Scott, HM., Eddie, S.L., Mitchell, R.T., Seckl, J.R., Drake, A.J., Smith, L.B., Anderson, R.A., and Sharpe, R.M. 2012. Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents. Public Library of Science One 7(5): e37064.

Welsh, M., Saunders, P.T.K., Fisken, M., Scott, H.M., Hutchison, G.R., Smith, L.R. and Sharpe, R.M. 2008. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. Journal of Clinical Investigation 118(4): 1479-1490.

Wudy, S.A., Schuler, G., Sanchez-Guijo, A., and Hartmann, M.F. 2018. The art of measuring steroids: Principles and practice of current hormonal steroid analysis. Journal of Steroid Biochemistry and Molecular Biology 179: 88–103.

Zhang, H., Zhou, Y., Xing, Z., Sah, R.K., Hu, J., and Hu, H. 2022. Androgen Metabolism and Response in Prostate Cancer Anti-Androgen Therapy Resistance. International Journal of Molecular Sciences 23: 13521. https://doi.org/10.3390/ijms232113521.

Zhou, J., Wang, Y., Wu, D., Wang, S., Chen, Z. Xiang, S., and Chan, F.L. 2021. Orphan nuclear receptors as regulators of intratumoral androgen biosynthesis in castration-resistant prostate cancer. Oncogene 40: 2625–2634.

NOTE: Italics symbolize edits from John Frisch