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Event: 2137

Key Event Title

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

Increase, Gonadotropins concentration in plasma

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

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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

Organ term

Organ term
blood plasma

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
hormone secretion	gonadotropin releasing neuron	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
Androgen receptor agonism leading to reproduction dysfunction	KeyEvent	Hongling Liu (send email)	Under development: Not open for comment. Do not cite
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

This Key Event represents increased gonadotropin levels in plasma. Gonadotropins are hormones in mammals that cue development of reproductive organs to maturity (Casarini and Simoni 2021; Howard 2021) and the different phases of the estrus cycle in rodents (Uenoyama et al. 2021). Gonadotropins are composed of two subunits: a 90-100 amino acid alpha subunit that is identical for all gonadotropins for a species, and a 105-150 amino acid beta subunit that are unique to each gonadotropin but exhibit large similarities in order to interact with alpha subunits (Cahoreau et al 2015). Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) are two gonadotropins released from the anterior pituitary gland (Howard 2021) resulting in increased gonadotropin concentrations in plasma.

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

Gonadotropin levels are generally measured from blood or urine samples by immunoassay or Western blotting (studies that utilized this approach include Adachi et al. 2007; Clarkson et al. 2008; Wang et al. 2014; Zhou et al. 2023). Commercial ELISA kits are available for Luteinizing hormone (e.g. Abcam AB303746 (human); Aviva OKCA00156 (mouse); ThermoFisher EHLH (human)) and Follicle-stimulating hormone (e.g. ThermoFisher EH202RB (human); ALPCO 11-FSHHU-E01 (human); ENZO ENZ-KIT108 (human). Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Real time PCR can be used to measure gonadotropin transcript abundance, which is an indirect – and only semi-quantitative indicator of gonadotropin hormone levels. Since gonadotropins share a common alpha subunit, focus is generally on the beta subunit (studies that utilized this approach include Schirman-Hildesheim et al. 2008; Bo et al. 2022; Oride et al. 2023).

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 both males and females as both sexes require gonadotropin signalling for hormone pathways.

Taxonomic: Primarily studied in laboratory rodents and humans. Plausible for most mammals due to conserved hormone pathways regulating hypothalamus-pituitary-gonadal axis processes. Gonadotropins widespread among vertebrates, including fish, amphibians, reptiles, birds, and mammals (Hollander-Cohen et al. 2021).

References

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

Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M, Takase K, Sugiura H, Ohtaki T, Matsumoto H, Uenoyama Y, Tsukamura H, Inoue K, Maeda K. 2007. Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. Journal of Reproduction and Development 53(2):367-378.

Bo T, Liu M, Tang L, Lv J, Wen J, Wang D. 2022. Effects of High-Fat Diet During Childhood on Precocious Puberty and Gut Microbiota in Mice. Frontiers in Microbiology 13: 930747.

Cahoreau C, Klett D, Combarnous Y. 2015. Structure-function relationships of glycoprotein hormones and their subunits' ancestors. Frontiers in Endocrinology 6: 26.

Casarini, L. and Simoni M. 2021. Recent advances in understanding gonadotropin signaling. Faculty Reviews 10: 41.

Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE. 2008. Kisspeptin–GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. Journal of Neuroscience 28(35): 8691–8697.

Hollander-Cohen L, Golan M, Levavi-Sivan B. 2021. Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary. International Journal of Molecular Sciences 22(12): 6478.

Howard, S.R. 2021. Interpretation of reproductive hormones before, during and after the pubertal transition—identifying health and disordered puberty. Clinical Endocrinolology 95: 702-715.

Oride A, Kanasaki H, Tumurbaatar T, Tumurgan Z, Okada H, Cairang Z, Satoru K. 2023. Impact of Ovariectomy on the Anterior Pituitary Gland in Female Rats. International Journal of Endocrinology 3143347.

Schirman-Hildesheim TD, Gershon E, Litichever N, Galiani D, Ben-Aroya N, Dekel N, Koch Y. 2008. Local production of the gonadotropic hormones in the rat ovary. Molecular and Cellular Endocrinology 282(1-2): 32-38.

Wang X, Chang F, Bai Y, Chen F, Zhang J, Chen L. 2014. Bisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice. Journal of Endocrinology 28(35): 201-213.

Zhou L, Ren Y, Li D, Zhou W, Li C, Wang Q, Yang X. 2023. Timosaponin AIII attenuates precocious puberty in mice through downregulating the hypothalamic-pituitary-gonadal axis. Acta Biochimica Polonica 70(1): 183-190.

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.