Zebrafish and steroids: What do we know and what do we need to know?

Tokarz, Janina; Möller, Gabriele; Angelis, Martin Hrabé de; Adamski, Jerzy

doi:10.1016/j.jsbmb.2013.01.003

Cited by 120 publications

(86 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The zebrafish has also emerged as a popular toxicological model for drug discovery, endocrinology, and environmental chemical defense studies James, 2011;Peterson and Macrae, 2012;Tokarz et al, 2013). The UDP-glucuronosyltransferases (UGTs) are an important class of diverse phase II drug-metabolizing and detoxification enzymes that affect the drug toxicity as well as its oral bioavailability (Wu et al, 2011;Meech et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the ZebrafishUgtRepertoire Reveals a New Class of Drug-Metabolizing UDP Glucuronosyltransferases

Wang¹,

Huang²,

Wu³

2014

Mol Pharmacol

View full text Add to dashboard Cite

The zebrafish genome contains a gene superfamily of 40 Ugt genes that can be divided into Ugt1, Ugt2, and Ugt5 families. Because the encoded zebrafish UDP glucuronosyltransferase (UGT) proteins do not display orthologous relationships to any of the mammalian and avian UGT enzymes based on molecular phylogeny, it is difficult to predict their substrate specificity. Here, we mapped their tissue-specific expression patterns. We showed that the zebrafish UGT enzymes can be glycosylated. We determined their substrate specificity and catalytic activity toward diverse aglycone substrates. Specifically, we measured mRNA levels of each of the 40 zebrafish Ugt genes in 11 adult tissues and found that they are expressed in a tissue-specific manner. Moreover, functional analyses with the donor of UDP glucuronic acid (UDPGA) for each of the 40 zebrafish UGT proteins revealed their substrate specificity toward 10 important aglycones. In particular, UGT1A1, UGT1A7, and UGT1B1 displayed good glucuronidation activities toward most phenolic aglycones (4-methylumbelliferone, 4-nitrophenol, 1-naphthol, bisphenol A, and mycophenolic acid) and the two carboxylic acids (bilirubin and diclofenac). Importantly, some members of the UGT5, a novel UGT family identified recently, are capable of glucuronidating multiple aglycones with the donor cofactor of UDPGA. In particular, UGT5A5, UGT5B2, and UGT5E1 glucuronidate phenols and steroids with high specificity toward steroid hormones of estradiol and testosterone and estrogenic alkylphenols 4-tert-octylphenol. These results shed new insights into the mechanisms by which fish species defend themselves against vast numbers of xenobiotics via glucuronidation conjugations and may facilitate the establishment of zebrafish as a model vertebrate in toxicological, developmental, and pathologic studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of the ZebrafishUgtRepertoire Reveals a New Class of Drug-Metabolizing UDP Glucuronosyltransferases

Wang¹,

Huang²,

Wu³

2014

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…The zebrafish Pr binds with high affinity (k in the nanomolar range) to the main endogenous progestogen in zebrafish, 17 ,20 -dihydroxy-4-pregnen-3-one (DHP) [39]. DHP is converted from 17-OH-progesterone by 20 -hydroxysteroid dehydrogenase (Hsd20b), an enzyme that has only been identified in teleosts [43,44]. The zebrafish Pr activated the mouse mammary tumor virus (MMTV) promoter in luciferase assays upon binding to DHP, progesterone, 17-OH-progesterone, 17 ,20 ,21-trihydroxy-4-pregnen-3-one (20 -S, another fishspecific endogenous progestogen), and the synthetic progestin promegestone (R5020) [39,40].…”

Section: The Zebrafish Prmentioning

confidence: 99%

“…Fish do not produce aldosterone, but it has been suggested that in fish DOC has a similar function to aldosterone in mammals [86]. DOC is putatively converted from progesterone by steroid 21-monooxygenase (cyp21a1), but the presence of this enzyme has not been demonstrated in zebrafish and has been poorly characterized in several other fish species [43,44]. Interestingly, the human MR antagonist spironolactone showed agonistic activity on the zebrafish Mr, whereas eplerenone and nimodipine acted as antagonists of the zebrafish Mr [85].…”

Section: The Zebrafish Mrmentioning

confidence: 99%

The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

Schaaf¹

2017

Nuclear Receptor Research

View full text Add to dashboard Cite

Abstract. Steroid hormones regulate a wide range of processes in our body, and their effects are mediated by steroid receptors. In addition to their physiological role, these receptors mediate the effects of endocrine disrupting chemicals (EDCs) and are widely used targets for dugs involved in the treatment of numerous diseases, ranging from cancer to inflammatory disorders. Over the last fifteen years, the zebrafish has increasingly been used as an animal model in steroid receptor research. Orthologues of all human steroid receptor genes appear to be present in zebrafish. All zebrafish steroid receptors have been characterized in detail, and their expression patterns have been analyzed. Functional studies have been performed using morpholino knockdown of receptor expression and zebrafish lines carrying mutations in one of their steroid receptor genes. To investigate the activity of the receptors in vivo, specific zebrafish reporter lines have been developed, and transcriptomic studies have been carried out to identify biomarkers for steroid receptor action. In this review, an overview of research on steroid receptors in zebrafish is presented, and it is concluded that further exploitation of the possibilities of the zebrafish model system will contribute significantly to the advancement of steroid receptor research in the next decade.

show abstract

“…To date, most of the steroidogenic enzymes have been cloned and their expression has been analysed by both PCR approaches and in situ hybridisation (Tokarz et al, 2013). The P450scc enzyme (cyp11a1) acts as the catalyst for the first and rate-limiting step in steroidogenesis, and is responsible for the conversion of cholesterol into pregnenolone.…”

Section: Introductionmentioning

confidence: 99%

“…The P450scc enzyme (cyp11a1) acts as the catalyst for the first and rate-limiting step in steroidogenesis, and is responsible for the conversion of cholesterol into pregnenolone. In teleosts (Tokarz et al, 2013), including the Japanese eel (Anguilla japonica; Ijiri et al, 2006), its gene expression and immunolocalization are located in the Leydig cells. One of the enzymes responsible for metabolising pregnenolone is the cytochrome P450c17 (cyp17) enzyme.…”

Section: Introductionmentioning

confidence: 99%

Molecular approaches related to the European eel (Anguilla anguilla) reproductive process

Morini¹

View full text Add to dashboard Cite

ACKNOWLEDGEMENTSEn primer lugar quiero dar las gracias a Johnny por haberme dado la oportunidad de realizar este doctorado. Muchas gracias por la ayuda y los buenos consejos prestados. Agradezco mucho tu comprensión y empatía cada vez que he estado malita.Gracias también a Luz, por tu buen humor y tu gran simpatía. Me has hecho sentir muy cómoda desde el principio y además me has convertido en fanática gatuna.David, muchas gracias por haber confiado en mi desde el principio, darme libertad en la realización de los experimentos y haber resuelto todas las dudas que iban surgiendo.Por otra parte quería dedicar un párrafo muy especial a mis primeros amigos españoles, mis preferidos y que a la vez eran mis compañeros de trabajo.Como podéis imaginar siempre es difícil llegar a otro país, lejos de la familia, de los amigos de la infancia y sin hablar el idioma. Vosotros me lo habéis hecho todo más fácil. He aprendido mucho a vuestro lado y he evolucionado mucho gracias a vosotros, de ser sepia (gracias Vic) a casi valenciana con acento francés. Me lo he pasado fenomenal entre las cervecitas del viernes, las excursiones del sábado, las inumerables comidas y cenas, nocheviejas, etc… Rosa, nunca olvidaré nuestra primera salida "Alcampo", tu cara mirándome fijamente mientras cojeabas y sonaba la música de tu móvil!!! Toda una historia… Y en nochevieja, que bien me lo pasé con mi compañera de cubatas y de "baño que pincha", mis vaqueros aún se acuerdan de aquella noche!! Pablo, mi traductor oficial de los Mojinos!! A ver si podemos ir a otro concierto pronto! Y volver a comer crêpes en Paris! Cara-crêpes! Vic, nada más volver de Japón me iniciaste a tu pasión… los pajaritos!! Las orejas de cerdo vinieron mucho más tarde ;-) Me descubriste este mundo y ahora veo los pajaritos con otro ojo (y otra oreja). Tú crees que otro petirrojo nos dará un concierto privado como el de Cazorla??Mamen, no sé ni por dónde empezar… Nunca olvidaré todo lo que has hecho por mí. Recuerdo al principio cuando casi sin conocernos me invitaste a tu cumpleaños junto a toda tu familia!. He disfrutado mucho todos los momentos que hemos pasado juntas estos años (entre las anguilas, el laboratorio, las vacaciones, las fallas, las nocheviejas, los fin des, paseos con bolt, cenas improvisadas...) Creo que he pasado más tiempo contigo que con Richard. Gracias por todo!!! También quiero dar las gracias a una gran cocinera y amiga, llamada Aquagamete, o Pepa, para los íntimos! Me han encantado nuestras comiditas y me ha ayudado mucho tenerte aquí. Además, gracias a ti he podido probar y disfrutar el mejor jamón del mundo! No olvido a los 2 últimos fichados: los vecinos alborayenses Chris y German. Continuaremos disfrutando de nuestras cervecitas y horchatitas después de una partida de volley-playa.Gracias al grupo de nutrición, Miguel, Ana, Silvia, Raquel, Sergio… con mención especial a Guillem por tu ayuda y tu valenciano perfecto (yo tenía complicado el resum en valenciá); y a Nacho, por tu ayuda con la portada y tu paciencia durante el final de mi tesis, ...

show abstract

Zebrafish and steroids: What do we know and what do we need to know?

Cited by 120 publications

References 146 publications

Characterization of the ZebrafishUgtRepertoire Reveals a New Class of Drug-Metabolizing UDP Glucuronosyltransferases

Characterization of the ZebrafishUgtRepertoire Reveals a New Class of Drug-Metabolizing UDP Glucuronosyltransferases

The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

Molecular approaches related to the European eel (Anguilla anguilla) reproductive process

Contact Info

Product

Resources

About