Differential ligand selectivity of androgen receptors α and β from Murray–Darling rainbowfish (Melanotaenia fluviatilis)

Bain, Peter A.; Ogino, Yukiko; Miyagawa, Shinichi; Iguchi, Taisen; Kumar, Anu

doi:10.1016/j.ygcen.2015.01.024

Cited by 20 publications

(12 citation statements)

References 64 publications

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“…We found that both CPA and CMA were strong antagonists of rfARβ, with potencies similar to that reported for the model non-steroidal antiandrogen, flutamide (Bain et al, 2015b). This is consistent with the well-characterized antagonism of the human AR by CPA and CMA (Raudrant and Rabe, 2003).…”

Section: In Vitro Activitiessupporting

confidence: 88%

“…Stable reporter gene assays were developed using dual antibiotics selection to ensure the maintenance of the transfected receptor expression vector and along with a selective luciferase reporter construct. Construction of the rainbowfish androgen receptor β (rfARβ) and progestogen receptor (rfPGR) stable reporter gene assays has been previously described (Bain et al, 2015b). Similar assays for rainbowfish estrogen receptor α (rfERα) and glucocorticoid receptor 2 (rfGR2) were developed using pcDNA3.1-based expression constructs and pGL4.26 luciferase reporter vectors containing suitable response elements (Bain et al,…”

Section: In Vitro Reporter Gene Assays Expressing Rainbowfish Nuclearmentioning

confidence: 99%

“…The agonistic activity of the selected compounds in the rainbowfish reporter gene assays was determined essentially according to the method of Bain et al (2015b). Briefly, cells were seeded into 96-well plates at a density of 10,000 cells/well in 100 µL exposure media (phenol red-free DMEM-F12 medium supplemented with 5% dextran-coated charcoalstripped fetal bovine serum [DCC-FBS], Eagles non-essential amino acids, 20 U/mL penicillin and 20 µg/mL streptomycin) and incubated overnight in a humidified atmosphere at 37 °C and 5% CO 2 .…”

Section: Manuscripts In Preparation)mentioning

confidence: 99%

“…They also showed cross-reactivity with other nuclear sex steroid receptors (Bain et al, 2015a;Ellestad et al, 2014;Pinter and Thomas, 1997). Similarly, progestins may have different interactions with human and fish AR (Bain et al, 2015a(Bain et al, , 2015bEllestad et al, 2014). Some progestins were found to have high endocrine disruption potency in fish (Fent, 2015;Kumar et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

et al. 2017

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Synthetic progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. Here, we focused on an unexplored antiandrogenic progestin, chlormadinone acetate (CMA), and the antiandrogenic progestin cyproterone acetate (CPA). The aim was to evaluate whether their in vitro interaction with human and rainbowfish (Melanotaenia fluviatilis) sex hormone receptors is similar. Furthermore, we investigated their activity in zebrafish (Danio rerio) eleuthero-embryos. First, we studied agonistic and antagonistic activities of CMA, CPA, and 17α-ethinylestradiol (EE2), in recombinant yeast expressing either the human progesterone (PGR), androgen (AR), or estrogen receptor. The same compounds were also investigated in vitro in a stable transfection cell system expressing rainbowfish nuclear steroid receptors. For human receptors, both progestins exhibited progestogenic, androgenic and antiestrogenic activity with no antiandrogenic or estrogenic activity. In contrast, interactions with rainbowfish receptors showed no progestogenic, but antiandrogenic, antiglucocorticoid, and some antiestrogenic activity. Thus, interaction with and transactivation of human and rainbowfish PGR and AR were distinctly different. Second, we analyzed transcriptional alterations in zebrafish eleuthero-embryos at 96 and 144h post fertilization after exposure to CPA, CMA, EE2, and binary mixtures of CMA and CPA with EE2, mimicking the use in oral contraceptives. CMA led to slight down-regulation of the ar transcript, while CPA down-regulated ar and pgr transcripts. EE2 exposure resulted in significant transcriptional alterations of several genes, including esr1, pgr, vtg1, cyp19b, and gonadotropins (fshb, lhb). The mixture activity of CMA and EE2 followed the independent action model, while CPA and EE2 mixtures showed additive action in transcriptional alterations. Third, we analyzed the interactions of binary mixtures of CMA and CPA, and of CMA and EE2 for their joint activity in vitro and in eleuthero-embryos. Both mixtures behaved according to the concentration addition model in their in vitro interaction with human and rainbowfish receptors, often showing antagonism. In zebrafish eleuthero-embryos, binary mixtures of CMA and EE2 showed the same expression patterns as EE2 alone, indicating an independent action in vivo. Our study demonstrates that CMA and CPA interact distinctly with human and rainbowfish receptors, suggesting that activities of these and possibly additional environmental steroids determined with yeast expressing human receptors cannot simply be translated to fish. The lack of agonistic activities of both progestins to rainbowfish PGR and AR is the probable reason for the low activity found in zebrafish eleuthero-embryos.

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Section: In Vitro Activitiessupporting

confidence: 88%

Section: In Vitro Reporter Gene Assays Expressing Rainbowfish Nuclearmentioning

confidence: 99%

Section: Manuscripts In Preparation)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

et al. 2017

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“…It should be emphasized, however, that although correlations between in vitro and in vivo data have been established , detection of in vitro hormone receptor activity does not immediately imply in vivo effects in exposed species. The sensitivity of mammalian hormone receptors (i.e., the human receptors used in the present study) to various ligands may be significantly different from corresponding receptors in aquatic vertebrates . In addition, different species of fish may show differences in sensitivity to environmental EDCs, which must be accounted for in environmental risk assessment.…”

Section: Discussionmentioning

confidence: 93%

Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent‐ receiving environment using a panel of in vitro bioassays

Roberts

Bain

Kumar

et al. 2015

Enviro Toxic and Chemistry

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Estrogenicity of sewage effluents, and related ecotoxicological effects in effluent-receiving environments, have been widely reported over the last 2 decades. However, relatively little attention has been given to other endocrine pathways that may be similarly disrupted by a growing list of contaminants of concern. Furthermore, the Australian evidence base is limited compared with those of Europe and North America. During a low dilution period in summer, the authors investigated multiple endocrine potencies in Australia's largest inland sewage treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent-receiving environment. This STP receives 900 L/s of mostly domestic wastewater from a population of 350 000, and contributes a high proportion of total flow in the lower catchment during dry periods. A panel of in vitro receptor-driven transactivation assays were used to detect (anti)estrogenic, (anti) androgenic, (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at various stages of the sewage treatment process. Total estrogenic and (anti)androgenic potency was removed after primary and/or secondary treatment; however, total removal efficiency for glucocorticoid potency was poorer (53-66%), and progestagenic potency was found to increase along the treatment train. Estrogenicity was detected in surface waters and bed sediments upstream and downstream of the effluent outfall, at maximum levels 10 times lower than low-hazard thresholds. Glucocorticoid and progestagenic activity were found to persist to 4 km downstream of the effluent outfall, suggesting that future research is needed on these endocrine-disrupting chemical categories in effluent-receiving systems.

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Mifepristone affects fertility and development in the sea urchin Paracentrotus lividus

Fabbrocini

Coccia

D’Adamo

et al. 2019

Molecular Reproduction Devel

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Drugs such as oral contraceptives and hormone replacement therapies are known to find their way into rivers, lakes and seas, and have the potential to affect reproduction and development of the wildlife. The knowledge of the reproductive mechanisms and their regulation in aquatic species is of fundamental importance for predicting and preventing the damage by the increasing release of such chemicals in the environment. Mifepristone, a synthetic steroid used as a drug for chemical abortion, works by blocking the effects of progesterone. Its presence in fresh and salt water has been reported, representing a danger for aquatic species. In this frame, we evaluated in both acute and chronic exposures, the effects of mifepristone on the reproductive performance of the sea urchin P. lividus. In both acute and chronic exposures, mifepristone did not affect the histological structure of the gonads. However, mifepristone administered to females caused the decrease of the percentage of normal developed plutei larvae compared with the control, whereas it did not alter sperm motility parameters and fertilization success in males. The immunohistological localization of progesterone receptor-like immunoreactivity on the plasma membrane of oocytes and ova and the molecular weight of a progesterone receptor-like immunoband identified by western blotting, are in agreement with a membrane progesterone receptor deducted from the genome sequence of the sea urchin Strongylocentrotus purpuratus and suggest that in P. lividus mifepristone actions may be mediated by a progesterone receptor. K E Y W O R D S embryo development, mifepristone, P. lividus, reproduction, sperm motility

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Differential ligand selectivity of androgen receptors α and β from Murray–Darling rainbowfish (Melanotaenia fluviatilis)

Cited by 20 publications

References 64 publications

Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent‐ receiving environment using a panel of in vitro bioassays

Mifepristone affects fertility and development in the sea urchin Paracentrotus lividus

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