Comparison of response to 17β‐estradiol and 17β‐trenbolone among three small fish species

Seki, Masanori; Fujishima, Saori; Nozaka, Toshiki; Maeda, Masanobu; Kobayashi, Kunio

doi:10.1897/05-647r.1

Cited by 104 publications

(88 citation statements)

References 25 publications

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“…Short-term (typically 21-d) assays with adult fish are being used by regulatory authorities throughout the world as a basis for identifying EDCs (Seki et al, 2006;U.S. Environmental Protection Agency, 2007;Organisation for Economic Cooperation and Development, 2009b).…”

Section: Discussionmentioning

confidence: 99%

“…Environmental Protection Agency, 2007;Organisation for Economic Cooperation and Development, 2009b). While some endocrine mechanisms are reliably detected in these assays, anti-androgens are more difficult to identify in an unambiguous fashion (Seki et al, 2006;Katsiadaki et al, 2006;Filby et al, 2007;U.S. Environmental Protection Agency, 2007;Organisation for Economic Cooperation and Development, 2009b).…”

Section: Discussionmentioning

confidence: 99%

“…Chemicals that inhibit steroidogenesis consistently decrease VTG levels in female fish. However, the suite of responses produced by anti-androgenic chemicals in sexually mature fish can be somewhat ambiguous, making it difficult to clearly diagnose this important pathway Katsiadaki et al, 2006;Seki et al, 2006;Filby et al, 2007;Organisation for Economic Cooperation and Development, 2009b). A wide variety of known or potential environmental contaminants, including some dicarboximide fungicides (e.g., vinclozolin), conazole fungicides (e.g., prochloraz), organochlorine insecticides (e.g., p,p -DDE), urea-based herbicides (e.g., linuron), polybrominated diphenyl ethers, and pharmaceuticals (e.g., flutamide) have been shown to bind to the AR, and cause anti-androgenic effects in vivo (Gray et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The basis of the approach lies in evaluating whether test chemicals block occurrence of an in vivo response mediated through the AR. Studies in our lab and elsewhere have shown that the synthetic androgen 17␤-trenbolone (TB) binds with high affinity to fish AR(s) and masculinizes female fish at concentrations in water in the range of 20-50 ng/L (Ankley et al, 2003;Wilson et al, 2004;Seki et al, 2006). In the fathead minnow, masculinization is manifested by a proliferation and thickening of the dorsal pad and the de novo development of craniofacial nuptial tubercles, external structures which can be visually detected and easily quantified ).…”

Section: Introductionmentioning

confidence: 99%

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Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model

et al. 2010

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a b s t r a c tVarious assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis. These assays can be sensitive and highly diagnostic for key mechanisms such as agonism of the estrogen and androgen receptors (ERs, ARs) and inhibition of steroid synthesis. However, most of the tests do not unambiguously identify AR antagonists. The purpose of this work was to explore the utility of a mixture test design with the fathead minnow (Pimephales promelas) for detecting different classes of EDCs including AR antagonists. Adults of both sexes were exposed via the water to EDCs with diverse mechanisms of action in the absence or presence of 17␤-trenbolone (TB), a potent AR agonist which masculinizes female fathead minnows. Similar to previous studies with the model AR antagonists flutamide and vinclozolin, exposure of females to the AR antagonist cyproterone acetate in the presence of TB decreased expression of an easily-observed masculinization response, nuptial tubercle formation. Mixture studies with TB and the model ER agonists, 17␣-ethinylestradiol and bisphenol A, also showed inhibition of tubercle formation in the females, but unlike the AR antagonists, the estrogens markedly induced synthesis of vitellogenin (VTG: egg yolk protein), particularly in males. The ER agonists also offset TB-induced depressions in plasma VTG concentrations in female fish. Additional mixture experiments were conducted with TB and triclocarban, an anti-microbial reported to enhance AR-mediated responses, or ammonia, a "negative control" with no known direct effects on HPG function. Neither chemical affected VTG status in males or females in the absence or presence of TB; however, both slightly enhanced TB-induced tubercle formation in females. Based on studies described herein and elsewhere with the fathead minnow, a TB co-exposure assay appears to be an effective approach for clearly identifying AR antagonists as well as potential EDCs with other relevant mechanisms of action.Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model

et al. 2010

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“…We were unable to measure circulating estrogens in our study, since the currently available methods lack the sensitivity required for this analysis in orchiectomized male rodents. However, in vitro evidence indicates that trenbolone and its primary metabolites are relatively nonestrogenic (30), and in vivo evidence demonstrates that trenbolone induces antiestrogenic effects in oviparous species (3,16,23,32,38,53). Additionally, it has been reported that trenbolone does not undergo aromatization due to its 3-oxotriene structure (46), although conflicting reports exist regarding the influence of trenbolone on circulating estrogens in mammalian species (24,26).…”

Section: E657mentioning

confidence: 99%

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

Yarrow

Conover

McCoy

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Yarrow JF, Conover CF, McCoy SC, Lipinska JA, Santillana CA, Hance JM, Cannady DF, VanPelt TD, Sanchez J, Conrad BP, Pingel JE, Wronski TJ, Borst SE. 17␤-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate. Am J Physiol Endocrinol Metab 300: E650 -E660, 2011; First published January 25, 2011; doi:10.1152/ajpendo.00440.2010.-Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17␤-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5␣-reduction to form more potent androgens. We tested the hypothesis that trenbolone-enanthate (TREN) might prevent orchiectomy-induced losses in muscle and bone and visceral fat accumulation without increasing prostate mass or resulting in adverse hemoglobin elevations. Male F344 rats aged 3 mo underwent orchiectomy or remained intact and were administered graded doses of TREN, supraphysiological testosterone-enanthate, or vehicle for 29 days. In both intact and orchiectomized animals, all TREN doses and supraphysiological testosterone-enanthate augmented androgen-sensitive levator ani/ bulbocavernosus muscle mass by 35-40% above shams (P Յ 0.001) and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses (P Ͻ 0.05) and visceral fat accumulation (P Ͻ 0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at sham levels in both intact and orchiectomized animals, whereas supraphysiological testosteroneenanthate and high-dose TREN elevated prostate mass by 84 and 68%, respectively (P Ͻ 0.01). In summary, low-dose administration of the non-5␣-reducible androgen TREN maintains prostate mass and hemoglobin concentrations near the level of shams while producing potent myotrophic actions in skeletal muscle and partial protection against orchiectomy-induced bone loss and visceral fat accumulation. Our findings indicate that TREN has advantages over supraphysiological testosterone and supports the need for future preclinical studies examining the viability of TREN as an option for androgen replacement therapy.

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Use of Medaka in Toxicity Testing

et al. 2009

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Small aquarium fishes are increasingly used as animal models, and one of these, Japanese Medaka (Oryzias latipes), is frequently utilized for toxicity testing. While these vertebrates have many similarities with their terrestrial counterparts, there are differences that must be considered if these organisms are to be used to their highest potential. Testing commonly may employ either the developing embryo or adults; both are easy to use and to work with. We present here three main protocols to illustrate the utility and breadth of toxicity testing possible using medaka fish. The first protocol assesses neurotoxicity in developing embryos. The second protocol describes the sexual genotyping of medaka to evaluate toxicant effects on sexual phenotype after treatment with endocrine disrupting chemicals. The third protocol assesses hepatotoxicity in adult fish after treatment with a model hepatotoxicant. The methods run the gamut from immunohistology through PCR to basic histological techniques.

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Comparison of response to 17β‐estradiol and 17β‐trenbolone among three small fish species

Cited by 104 publications

References 25 publications

Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model

Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

Use of Medaka in Toxicity Testing

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