Key Event Overview
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AOPs Including This Key Event
|AOP Name||Event Type||Essentiality|
|Androgen receptor agonism leading to reproductive dysfunction||KE||Moderate|
Level of Biological Organization
How this Key Event works
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
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., ELISAs, RIAs, 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.
Evidence Supporting Taxonomic Applicability
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.
- Norris DO. 2007. Vertebrate Endocrinology. Fourth ed. New York: Academic Press.
- 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.
- 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.
- Oakley AE, Clifton DK, Steiner RA. 2009. Kisspeptin signaling in the brain. Endocrine reviews 30(6): 713-743.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.