Key Event Title
|Level of Biological Organization|
Key Event Components
|androgen biosynthetic process||11-Keto-testosterone||decreased|
Key Event Overview
AOPs Including This Key Event
|teleost fish||teleost fish||High||NCBI|
|Homo sapiens||Homo sapiens||High||NCBI|
|Adult, reproductively mature||High|
Key Event Description
11-ketotestosterone (11KT) is the dominant androgen in teleost fish. It is synthesized from testosterone using the enzymes CYP11b1 and HSD11b (Yazawa et al., 2008; Swart et al., 2013).
How It Is Measured or Detected
11KT production can be measured in an ex vivo steroidogenesis assay using the organism's gonad after it has been exposed to a compound.
The concentration of 11KT can be measured in a radioimmunoassay or enzyme-linked immunosorbent assay (ELISA).
Several papers show that in fish, 11KT is correlated with testosterone levels (Spanò et al., 2004; Maclatchy & Vanderkraak, 1995; Lorenzi et al., 2008).
Domain of Applicability
Taxanomic Applicability: Most understand of 11KT comes from studies including teleost fish, including several studies using the listed stressors. Some studies have measured 11KT in sharks of the order Carcharhiniformes, but there is less research in this area (Manire et al., 1999; Garnier et al., 1999; Mills et al., 2010)
Sex Applicability: Males and females use the same biological processes to produce steroids. However, sexual dimorphism in 11KT production varies between species. In humans, plasma levels of 11KT do not differ between sexes (Imamichi et al., 2016). In Zebrafish, gonad levels of 11KT are approximately two magnitudes higher in males than females (Wang & Orban, 2007). Of the 30 other fish species sampled by Lokman et al. (2002), 11KT levels are typically dramatically lower in females than in males, but a few species of the order Perciformes show no sexual dimorphism.
Life Stage Applicability: Lokman et al. (2002) measured plasma levels of 11-KT in several species of juvenile and adult fish. Levels of 11KT in juveniles are similar to levels in females regardless of if the species shows sexual dimorphism in 11KT levels. 11KT can be measured in fish larvae however individuals must be pooled for sufficient sample size (Hattori et al., 2009)
Evidence for Perturbation by Stressor
Beta-sitosterol causes a dose-depended reduction in 11KT in male goldfish (MacLatchy & Van Der Kraak 1995)
Bezafibrate reduces 11-KT in the plasma of adult male zebrafish (Velasco-Santamaría et al. 2011)
Gemfibrozil reduces 11KT in the plasma of adult male medaka (Lee et al. 2019)
Hattori, R.S. et al. (2009) “Cortisol-induced masculinization: Does thermal stress affect gonadal fate in pejerrey, a teleost fish with temperature-dependent sex determination?”, PLoS ONE, Vol. 4(8), pp. 1-7. doi:10.1371/journal.pone.0006548
Imamichi, Y. et al. (2016) “11-Ketotestosterone is a major androgen produced in human gonads”, The Journal of Clinical Endocrinology & Metabolism, Vol. 101(10), Oxford Academic, pp. 3582-3591. https://doi.org/10.1210/jc.2016-2311
Lee, G. et al. (2019) “Effects of gemfibrozil on sex hormones and reproduction related performances of Oryzias latipes following long-term (155 d) and short-term (21 d) exposure”, Ecotoxicology and Environmental Safety, Vol. 173, Elsevier, pp. 174-181. https://doi.org/10.1016/j.ecoenv.2019.02.015
Lokman, P.M. et al. (2002) “11-Oxygenated androgens in female teleosts: prevalence, abundance, and life history implications”, General and Comparative Endocrinology, Vol. 129, Academic Press, pp. 1-12. doi: 10.1016/s0016-6480(02)00562-2
Lorenzi, V. et al. (2008) “Diurnal patterns and sex differences in cortisol, 11-ketotestosterone, testosterone, and 17β-estradiol in the bluebanded goby (Lythrypnus dalli)”, General and Comparative Endocrinology, Vol. 155(2)., Elsevier, pp. 438-446. https://doi.org/10.1016/j.ygcen.2007.07.010
MacLatchy, D.L. and G.J. Vanderkraak (1995) “The phytoestrogen β-sitosterol alters the reproductive endocrine status of goldfish”, Toxicology and Applied Pharmacology, Vol. 134(2), Elsevier, pp. 305-312. https://doi.org/10.1006/taap.1995.1196
Spanó, L. et al. (2004) “Effects of atrazine on sex steroid dynamics, plasma vitellogenin concentration and gonad development in adult goldfish (Carassius auratus)”, Aquatic Toxicology, Vol. 66(4), Elsevier, pp. 369-379. https://doi.org/10.1016/j.aquatox.2003.10.009
Swart, A.C. et al. (2013) “11β-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5α-reductase yielding 11β-hydroxy-5α-androstanedione”, The Journal of Steroid Biochemistry and Molecular Biology, Vol 138, Elsevier, pp. 132-142. https://doi.org/10.1016/j.jsbmb.2013.04.010
Velasco-Santamaría, Y.M. et al. (2011) “Bezafibrate, a lipid-lowering pharmaceutical, as a potential endocrine disruptor in male zebrafish (Danio rerio)”, Aquatic Toxicology, Vol. 105, Elsevier, pp. 107-118. doi:10.1016/j.aquatox.2011.05.018
Wang, X.G., L. Orban (2007) “Anti-Müllerian hormone and 11β-hydroxylase show reciprocal expression to that of aromatase in the transforming gonad of zebrafish males”, Developmental Dynamics, Vol 236(5), Wiley-Liss, pp. 1329-1338. https://doi.org/10.1002/dvdy.21129
Yazawa, T. (2008) “Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: Conservation and evolution of the androgen metabolic pathway”, Endocrinology, Vol. 149(4), Oxford Academy, pp. 1786-1792. https://doi.org/10.1210/en.2007-1015