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Event: 1047

Key Event Title

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

Increased, secretion of GnRH from hypothalamus

Short name

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Biological Context

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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
gonadotropin releasing neuron

Organ term

Organ term
hypothalamus

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 Hormone	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
Antiestrogens and ovarian adenomas/granular cell tumors	KeyEvent	Charles Wood (send email)	Under Development: Contributions and Comments Welcome
Hypothalamic estrogen receptors inhibition leading to ovarian cancer	KeyEvent	Kalyan Gayen (send email)	Under development: Not open for comment. Do not cite	Under Development
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

Gonadotropin-releasing hormone (GnRH) is a key signalling hormone in the hypothalamus- pituitary-gonadal (HPG) axis in mammals produced by the hypothalamus. Gonadotropin-releasing hormone is a peptide hormone composed of 10 amino acids (Hassanein et al. 2024). The C terminal (Pro-Gly-NH2) is involved in receptor binding, with the N-terminal (pGlu-His-Trp-Ser) involved in receptor activation (Hassanein et al. 2024). Increased levels of GnRH occur due to increased secretion from the hypothalamus.

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

GnRH can be measured via immunoassay or Western blotting (studies that utilized this approach include Clarkson et al. 2008; Kriszt et al. 2015; Bo et al. 2022), and include commercially available ELISA kits (e.g. Elabscience E-EL-0071 (universal; no cross-species reactivity); Assay Genie HUFI02509 (human); Cusabio CSB-E06880h (human); Biomatik EKC39138-96T (rat)). Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Real time PCR can be used to measure GnRH transcript abundance, which is an indirect – and only semi-quantitative indicator of GnRH hormone levels (studies that utilized this approach include Wang et al. 2014; Kriszt et al. 2015; Zhou 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 GnRH signalling for regulation of various 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. GnRH widespread among vertebrates, including amphibians, reptiles, birds, and mammals (Duan and Allard 2020).

References

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

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.

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.

Duan C, Allard J. 2020. Gonadotropin-releasing hormone neuron development in vertebrates. General and Comparative Endocrinology. 292: 113465

Hassanein, E.M., Szelényi, Z., Szenci, O. 2024. Gonadotropin-Releasing Hormone (GnRH) and Its Agonists in Bovine Reproduction I: Structure, Biosynthesis, Physiological Effects, and Its Role in Estrous Synchronization. Animals 14: 1473.

Kriszt R, Winkler Z, Polyak A, Kuti D, Molnar C, Hrabovszky E, Kallo I, Szoke Z, Ferenczi S, Kovacs KJ. 2015. Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling. Endocrinology 156(11): 3996-4007.

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.