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: 1610

Key Event Title

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

Reduction, dehydroepiandrosterone

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

Reduction, DHEA

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
Tissue

Organ 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

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

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
Cyp17A1 inhibition leads to undescended testes in mammals	KeyEvent	Bérénice COLLET (send email)	Open for citation & comment

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	High	NCBI

Life Stages

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

Life stage	Evidence
All life stages	High

Sex Applicability

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

Term	Evidence
Mixed	High

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

Dehydroepiandrosterone (DHEA) is defined as an obligatory intermediate in sex steroid biosynthesis being the precursor of steroid hormones like testosterone and estradiol.

The synthesis of DHEA is facilitated by the enzyme CYP17A1, which converts the direct precursor 17-OH-pregnenolone into DHEA through the 17,20-lyase reaction. DHEA can be converted by 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) to androstenedione or through 17-beta-hydroxysteroid dehydrogenase (17-beta-HSD) to androstenediol and finally steroid sulfotransferases can sulfate DHEA into DHEA-S (W. Miller, 1988; W. L. Miller & Auchus, 2011; Naamneh Elzenaty et al., 2022).

All these processes affect levels of DHEA. For instance, a chemically induced reduction in the upstream substrates can result in a decrease in DHEA level, specific enzyme inhibition of the CYP17A1 lyase reaction can decrease DHEA levels, downstream induction of 3-beta-HSD or 17-beta-HSD activity or expression may lead to less DHEA, as well as increased sulfation.

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

There is currently (2023) no OECD test guideline for the measurement of DHEA.

DHEA can be fractionated using High Performance Liquid Chromatography. After separation, DHEA levels can be quantified using immunoassays such as ELISA or Radio Immuno Assay (RIA) or mass spectrometry.

Considerations for measurement of hormone levels have been described (ECHA/EFSA, 2018; Stanislaus et al., 2012).

Domain of Applicability

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

This KE is applicable for both sexes, across developmental stage into adulthood, mainly in steroidogenic tissue, but also other tissues.

Taxonomic applicability.

There are species differences in DHEA synthesis, as the upstream lyase reaction, facilitated by CYP17A1, predominantly converts 17-OH-pregnenolone to DHEA in humans and primates, whereas the lyase reaction from 17-OH progesterone to androstenedione mainly takes place in rodents (Lawrence et al., 2022).

Life stage applicability

Fetal and adult adrenal cortex synthesize DHEA. The fetal liver and the placenta also contribute to production, though to a minor degree. Serum DHEA levels are low in early childhood and increase around adrenarche at age 8-10 years (Chatuphonprasert et al., 2018; W. L. Miller & Auchus, 2011).

Sex applicability

DHEA is expressed and essential in both sexes (Chatuphonprasert et al., 2018; W. L. Miller & Auchus, 2011).

References

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

Chatuphonprasert, W., Jarukamjorn, K., & Ellinger, I. (2018). Physiology and pathophysiology of steroid biosynthesis, transport and metabolism in the human placenta. In Frontiers in Pharmacology (Vol. 9, Issue SEP). Frontiers Media S.A. https://doi.org/10.3389/fphar.2018.01027

ECHA/EFSA. (2018). Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. EFSA Journal, 16(6). https://doi.org/10.2903/j.efsa.2018.5311

Gilep, A. A., Sushko, T. A., & Usanov, S. A. (2011). At the crossroads of steroid hormone biosynthesis: The role, substrate specificity and evolutionary development of CYP17. In Biochimica et Biophysica Acta - Proteins and Proteomics (Vol. 1814, Issue 1, pp. 200–209). https://doi.org/10.1016/j.bbapap.2010.06.021

Lawrence, B. M., O’Donnell, L., Smith, L. B., & Rebourcet, D. (2022). New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice. In International Journal of Molecular Sciences (Vol. 23, Issue 24). MDPI. https://doi.org/10.3390/ijms232415555

Miller, W. (1988). Miller_Molecualr Biology of steroid hormone synthesis_1988. Endrocrine Reviews, 9(3).

Miller, W. L., & Auchus, R. J. (2011). The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews, 32(1), 81–151. https://doi.org/10.1210/er.2010-0013

Naamneh Elzenaty, R., du Toit, T., & Flück, C. E. (2022). Basics of androgen synthesis and action. In Best Practice and Research: Clinical Endocrinology and Metabolism (Vol. 36, Issue 4). Bailliere Tindall Ltd. https://doi.org/10.1016/j.beem.2022.101665

Stanislaus, D., Andersson, H., Chapin, R., Creasy, D., Ferguson, D., Gilbert, M., Rosol, T. J., Boyce, R. W., & Wood, C. E. (2012). Society of Toxicologic Pathology Position Paper: Review Series: Assessment of Circulating Hormones in Nonclinical Toxicity Studies: General Concepts and Considerations. Toxicologic Pathology, 40(6), 943–950. https://doi.org/10.1177/0192623312444622