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: 2402

Key Event Title

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

Increased, estradiol (E2) production in ovaries

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

Increased, E2 production in ovaries

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

Organ term
ovarian follicle

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 hormone biosynthetic process	17beta-estradiol	increased

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
Activation, ERα leads to persistent vaginal cornification via increased kisspeptin	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
Adult, reproductively mature	Moderate
Juvenile	Moderate

Sex Applicability

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

Term	Evidence
Unspecific	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

Production of estradiol (E2) by the ovaries has been well-established by the two-cell, two gonadotropin model of steroid biosynthesis (for review see Drummond 2006; Kimura et al. 2007; Palermo 2007; Beevors et al. 2024). Luteinizing hormone stimulates steroid production in theca cells, with follicle-stimulating hormone stimulates steroid production in granulosa cells, resulting in increased estradiol production in ovaries.

Table 1: List of steroid synthesis enzymes with identifier of enzyme (Uniprot, 2025).

*Enzyme*	*Identifier*
Steroidogenic acute regulatory protein, mitochondrial (STAR)
Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A)	EC:1.14.15.6
3 beta-hydroxysteroid dehydrogenase (3B-HSD)	EC:1.1.1.145
Steroid 17-alpha-hydroxylase (CYP17A1)	EC:1.14.14.19
17-beta-hydroxysteroid dehydrogenase (17B-HSD)	EC:1.1.1.105
Aromatase (CYP19A1)	EC:1.14.14.14
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)	EC:1.3.1.22

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

Estradiol can be measured via immunoassay, mass spectrometry or Western blotting (Rosner et al. 2013; studies that utilized this approach include Sashida and Johnson 1976; Spears et al. 1998; Li et al. 2008; Murray et al. 2008; Gan et al. 2024), and include commercially available ELISA kits (e.g. Neogen 402110; ALPCO 11-ESTHU-E01; Cayman Chemical 501890). Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Since estradiol is generally synthesized from other steroids, real time PCR is generally not used, but transcription of key steroid biosynthesis genes, particularly cyp19 (aromatase) would be an indirect – and only semi-quantitative indicator of potential changes in estradiol hormone levels.

Enzymes involved in steroid biosynthesis in the ovaries can also be studied via immunoassay, Western blotting, or real time PCR (studies that utilized this approach include Li et al. 2008; Gan et al. 2024).

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: Adult, reproductively mature, juveniles.

Sex: Applies to females as specific to ovaries.

Taxonomic: Primarily studied in laboratory rodents and humans. Plausible for most mammals due to conserved hormone pathways regulating hypothalamus-pituitary-gonadal axis processes. Estradiol production in ovaries is widespread among vertebrates, including mammals (Bondesson et al. 2015), birds (Hanlon et al. 2022), fish (Li et al. 2019), reptiles (Cruz-Cano et al. 2023), and amphibians (Bondesson et al. 2015).

References

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

Beevors LI, Sundar S, Foster PA. 2024. Steroid metabolism and hormonal dynamics in normal and malignant ovaries. Essays in Biochemistry 68(4): 491-507.

Bondesson M, Hao R, Lin CY, Williams C, Gustafsson JA. 2015. Estrogen receptor signaling during vertebrate development. Biochimica et Biophysica Acta 1849(2): 142-151.

Cruz-Cano NB, Sanchez-Rivera UA, Alvarez-Rodriguez C, Cardenas-Leon M, Martinez-Torres M. 2023. Sex steroid receptors in the ovarian follicles of the lizard Sceloporus torquatus. Zygote. 31(4): 386-392.

Drummond AE. 2006. The role of steroids in follicular growth. Reproductive Biology and Endocrinology 4:16.

Gan H, Lan H, Hu Z, Zhu B, Sun L, Jiang Y, Wu L, Liu J, Ding Z, Ye X. 2024. Triclosan induces earlier puberty onset in female mice via interfering with L-type calcium channels and activating Pik3cd. Ecotoxicology and Environmental Safety 269: 115772.

Hanlon C, Ziezold CJ, Bedecarrats GY. 2022. The Diverse Roles of 17β-Estradiol in Non-Gonadal Tissues and Its Consequential Impact on Reproduction in Laying and Broiler Breeder Hens. Frontiers in Physiology 13: 942790.

Kimura S, Matsumoto T, Matsuyama R, Shiina H, Sato T, Takeyama K, Kato S. 2007. Androgen receptor function in folliculogenesis and its clinical implication in premature ovarian failure. Trends in Endocrinology and Metabolism 18(5): 183-189.

Li M, Sun L, Wang D. 2019. Roles of estrogens in fish sexual plasticity and sex differentiation. General and Comparative Endocrinology 277: 9-16.

Li Z, Li T, Leng Y, Chen S, Liu Q, Feng J, Chen H, Huang Y, Zhang Q. 2018. Hormonal changes and folliculogenesis in female offspring of rats exposed to cadmium during gestation and lactation. Environmental Pollution 238: 336-347.

Murray AA, Swales AK, Smith RE, Molinek MD, Hillier SG, Spears N. 2008. Follicular growth and oocyte competence in the in vitro cultured mouse follicle: effects of gonadotrophins and steroids. MHR-Basic Science of Reproductive Medicine 14(2): 75-83.

Palermo R. 2007. Differential actions of FSH and LH during folliculogenesis. Reproductive BioMedicine Online 15(3): 326-337.

Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME. 2013. Challenges to the measurement of estradiol: an endocrine society position statement. The Journal of Clinical Endocrinology and Metabolism. 98(4): 1376-1387.

Sashida T, Johnson DC. 1976. Stimulation of the estrogen synthesizing system of the immature rat ovary by exogenous and endogenous gonadotropins. Steroids 27(4): 469-79.

Spears N, Murray AA, Allison V, Boland NI, Gosden RG. 1998. Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro. Journal of Reproduction and Fertility 113(1): 19-26.

The UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025. https://www.uniprot.org/ (retrieved 2 November 2025).

NOTE: Italics indicate edits from John Frisch January 2026. A full list of updates can be found in the Change Log on the View History page.