Mammalian glucocorticoid metabolites act as androgenic endocrine disruptors in the medaka (Oryzias latipes)

Abstract

Glucocorticoid metabolites enter the aquatic environment via mammalian excrements. Molecular structures of their C19O3 metabolites strongly resemble the major fish androgen 11-ketotestosterone. Therefore, we tested the hypothesis that the cortisol metabolite 5alpha-androstan-3,11,17-trione acts similarly to 11-ketotestosterone by employing a fish screening assay for endocrine-active substances. After 21 d, both 11-oxygenated compounds had masculinized sex characteristics of the anal fin in female medaka in a dose-dependent manner.

Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment

“…High concentrations of dexamethasone negatively affected reproduction (LaLone et al, 2012). A cortisol metabolite acted similarly to 11-ketotestosterone leading to masculinization of female medaka (Grillitsch et al, 2010). Whether the effects of glucocorticoids are due to metabolites or due to interactions of parent compounds and metabolites to different steroid hormone receptors, including AR and PR, remains to be shown.…”

Endocrine Disrupting Compounds Affecting Corticosteroid Signaling Pathways in Czech and Swiss Waters: Potential Impact on Fish

“…[7][8][9] The exposure to GCs can lead to growth reduction, 7 immunosuppression, 7,10 decreased regenerative capacity, 11 increased plasma glucose levels, 12 reduced fecundity, 13 and fish masculinization. 12,14,15 Many compounds can indirectly interfere with the corticosteroid signaling pathway by modulating gene expression and activity of enzymes involved in the production and metabolism of corticosteroids. For example, suppression of the steroidogenic acute regulatory gene (StAR) may affect steroidogenesis in general; 21-hydroxylase (CYP21) inhibition can lead to reduced cortisol synthesis and increased androgen synthesis; inhibiton of 11β-hydroxylase (CYP11B1) may block the last step of cortisol synthesis; disruption of 11β-HSD1 and 11β-HSD2, that convert cortisone to cortisol and vice versa, can cause hormonal disbalances.…”

Brain nonapeptide and gonadal steroid responses to deprivation of heterosexual contact in the black molly

“…This suggests that high-density stress plays some role in promoting the process of masculinization. In some fish species, cortisol or its metabolites produced and secreted during stress cause masculinization of females or induce sex change ( Hattori et al, 2009 ; Grillitsch et al, 2010 ), probably because the molecular structure of glucocorticoids and 11-KT are similar. As demonstrated during high temperature-induced masculinization in several fish species, cortisol can also promote 11-KT production in gonads ( Fernandino et al, 2012 ).…”