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Event: 129

Key Event Title

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

Reduction, Gonadotropins, circulating concentrations

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
Organ

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
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
	Luteinizing hormone	decreased
	Follicle stimulating hormone	decreased

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 reproductive dysfunction	KeyEvent	Stephen Edwards (send email)	Open for citation & comment	WPHA/WNT Endorsed

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

Life Stages

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

Life stage	Evidence
Not Otherwise Specified	Not Specified

Sex Applicability

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

Term	Evidence
Unspecific	Not Specified

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 (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) secretion from the pituitary is a key regulator of gonadal steroid biosynthesis. LH and FSH are heterodimeric glycoproteins composed of a hormone-specific beta subunit and a common alpha subunit (Norris 2007). The subunits are synthesized in pituitary gonadotropes and stored in secretory vesicles. Gonadotropin secretion by pituitary gonadotropes is regulated via gonadotropin releasing hormone (GnRH) signaling from the hypothalamus as well as by intrapituitary regulators of gonadotropin expression (e.g., activin, follistatin, inhibin) (Norris 2007; Habibi and Huggard 1998).

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

Circulating concentrations of gonadotropins in humans and common mammalian models (e.g., rodents, many livestock species) can be directly measured using either commercial or custom immunoassays (e.g., enzyme-linked immunosorbent assays, radioimmunoassays, etc.).
Similar immunoassay-based methods have been developed for quantifying gonadotropins in fish (e.g., (Govoroun et al. 1998; Amano et al. 2000; Kah et al. 1989; Prat et al. 1996)). However, at present, antibodies specific for distinguishing LH and FSH are only available for a limited number of species, primarily salmonids (Levavi-Sivan et al. 2010).
Expression of mRNAs coding for luteinizing hormone beta subunit (lhb) and follicle-stimulating hormone beta subunit (fshb) tend to fluctuate in parallel in repeat-spawning fish and plasma concentrations LH and FSH in tilapia were also shown to fluctuate in parallel (reviewed in (Levavi-Sivan et al. 2010). Consequently, the two gonadotropins are treated non-specifically for the purposes of the current key event.
For small fish species limited plasma volumes relative to the sensitivity of the available immunoassay methods may impose limits on the ability to measure this key event directly and reliably.

Domain of Applicability

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

A functional hypothalamic-pituitary-gonadal axis involving GnRH and gonadotropin-mediated regulation of reproductive functions is a vertebrate trait (Sower et al. 2009). The taxonomic applicability of this key event is limited to chordates.

References

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

Amano M, Iigo M, Ikuta K, Kitamura S, Yamada H, Yamamori K. 2000. Roles of melatonin in gonadal maturation of underyearling precocious male masu salmon. General and comparative endocrinology 120(2): 190-197.
Cheng GF, Yuen CW, Ge W. 2007. Evidence for the existence of a local activin follistatin negative feedback loop in the goldfish pituitary and its regulation by activin and gonadal steroids. The Journal of endocrinology 195(3): 373-384.
Govoroun M, Chyb J, Breton B. 1998. Immunological cross-reactivity between rainbow trout GTH I and GTH II and their alpha and beta subunits: application to the development of specific radioimmunoassays. General and comparative endocrinology 111(1): 28-37.
Habibi HR, Huggard DL. 1998. Testosterone regulation of gonadotropin production in goldfish. Comparative biochemistry and physiology Part C, Pharmacology, toxicology & endocrinology 119(3): 339-344.
Kah O, Pontet A, Nunez Rodriguez J, Calas A, Breton B. 1989. Development of an enzyme-linked immunosorbent assay for goldfish gonadotropin. Biology of reproduction 41(1): 68-73.
Levavi-Sivan B, Bogerd J, Mananos EL, Gomez A, Lareyre JJ. 2010. Perspectives on fish gonadotropins and their receptors. General and comparative endocrinology 165(3): 412-437.
Norris DO. 2007. Vertebrate Endocrinology. Fourth ed. New York: Academic Press.
Oakley AE, Clifton DK, Steiner RA. 2009. Kisspeptin signaling in the brain. Endocrine reviews 30(6): 713-743.
Prat F, Sumpter JP, Tyler CR. 1996. Validation of radioimmunoassays for two salmon gonadotropins (GTH I and GTH II) and their plasma concentrations throughout the reproductivecycle in male and female rainbow trout (Oncorhynchus mykiss). Biology of reproduction 54(6): 1375-1382.
Sower SA, Freamat M, Kavanaugh SI. 2009. The origins of the vertebrate hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) endocrine systems: new insights from lampreys. General and comparative endocrinology 161(1): 20-29.
Trudeau VL, Spanswick D, Fraser EJ, Lariviére K, Crump D, Chiu S, et al. 2000. The role of amino acid neurotransmitters in the regulation of pituitary gonadotropin release in fish. Biochemistry and Cell Biology 78: 241-259.
Trudeau VL. 1997. Neuroendocrine regulation of gonadotropin II release and gonadal growth in the goldfish, Carassius auratus. Reviews of Reproduction 2: 55-68.