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Event: 2318

Key Event Title

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

Decreased 3-beta-HSD activity

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

Decreased 3βHSD activity

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Biological Context

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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

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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

3-beta-Hydroxysteroid dehydrogenase (3-beta-HSD) is a crucial enzyme in the steroidogenesis pathway, responsible for converting hydroxysteroids to ketosteroids. More specifically, 3-beta-HSD catalyzes the conversion of pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone (DHEA) to progesterone, 17-OH-progesterone, and androstenedione, respectively (Ye et al., 2014).

3-beta-HSD enzymes are membrane-bound and located in both mitochondrial and microsomal membranes. There are species-dependent differences for 3-beta-HSD enzymes, with mice having six isoforms and rats four (Zhu et al., 2019). In humans, two isoforms of 3-beta-HSD have been identified: 3-beta-HSD1 and 3-beta-HSD2. 3-beta-HSD1 is primarily found in the placenta, whereas 3-beta-HSD2 is predominantly located in gonadal tissues and adrenal glands. These isoforms differ in their affinities for steroid substrates, with 3-beta-HSD1 having a lower substrate affinity (Ye et al., 2014).

As 3-beta-HSD is responsible for the production of several steroids, its decrease can affect hormonal homeostasis. A model simulation has been developed, to predict the effects of 3-beta-HSD activity changes on the levels of substrates and products (Nguyen et al., 2012).

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 no standardized method to measure 3-beta-HSD activity. However, the activity can be assessed through various experimental approaches. These methods typically involve using a substrate derived from cell lines, tissues expressing the enzyme, or a purified enzyme preparation. Enzyme activity is commonly measured using spectrophotometric assays, by measuring the absorbance of NADH, which is part of the reaction, or using liquid chromatography-mass spectrometry to quantify the steroid products (Shivanandappa and Venkatesh, 1997).

Domain of Applicability

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

3-beta-HSD is essential for steroidogenesis in vertebrates, this KE is focused on mammals. The different 3-beta-HSD isoforms display tissue-specific expression and are involved in steroidogenesis from fetal life to adulthood in both sexes (Rasmussen et al., 2013).

References

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

Nguyen, P.T.T., Lee, R.S.F., Conley, A.J., Sneyd, J., Soboleva, T.K., 2012. Variation in 3β-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis. Journal of Steroid Biochemistry and Molecular Biology 128, 12–20. https://doi.org/10.1016/j.jsbmb.2011.10.003

Rasmussen, M.K., Ekstr, B., Zamaratskaia, G., 2013. Regulation of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase: A review. Int J Mol Sci. https://doi.org/10.3390/ijms140917926

Shivanandappa, T., Venkatesh, S., 1997. A Colorimetric Assay Method for 3b-Hydroxy-5-steroid Dehydrogenase, ANALYTICAL BIOCHEMISTRY.

Ye, L., Guo, J., Ge, R.S., 2014. Environmental Pollutants and Hydroxysteroid Dehydrogenases, in: Vitamins and Hormones. Academic Press Inc., pp. 349–390. https://doi.org/10.1016/B978-0-12-800095-3.00013-4

Zhu, Q., Pan, P., Chen, X., Wang, Y., Zhang, S., Mo, J., Li, X., Ge, R.S., 2019. Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5,4-isomerase 1: Identity, regulation and environmental inhibitors. Toxicology. https://doi.org/10.1016/j.tox.2019.152253