{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T07:37:09Z","timestamp":1772350629624,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"crossref","award":["EDDHC113001"],"award-info":[{"award-number":["EDDHC113001"]}],"id":[{"id":"10.13039\/501100004738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Androgen receptor (AR) signaling is crucial for mediating male-typical behaviors across vertebrates. Enzalutamide (ENZ) and apalutamide (APA) are two second-generation androgen receptor inhibitors (SGARIs) that have been primarily used in the treatment of prostate cancer. However, these drugs still possess side effects, and there remains limited information regarding their behavioral and neurophysiological impacts following chronic exposure in non-mammalian animal models, particularly in fish. Thus, this study aimed to evaluate the behavioral alterations in adult male zebrafish (Danio rerio) following exposure to specific AR blockers (ENZ and APA) and an activator, dihydrotestosterone (DHT), to provide a comprehensive comparison between each tested drug. Adult male zebrafish were exposed via aqueous immersion to each compound at a 1 ppm concentration for ~2 weeks and were subjected to a battery of behavioral tests. From the results, both AR blockers were found to slightly compromise fish locomotion, with contrary results observed in DHT-treated fish, which displayed an increased locomotor activity together with slight alterations in fish exploratory behaviors. Furthermore, ENZ also caused a tightened shoal formation in zebrafish, while exposure to APA was observed to slightly diminish the fear response of fish. On the other hand, the DHT-treated group displayed a higher level of aggression compared to the vehicle control group. In conclusion, functional modulation of androgen receptor signaling leads to significant alterations in male zebrafish behavior, particularly affecting fear responses, aggression, and anxiety-related behaviors. We believe that these findings could contribute to a deeper understanding of the relationship between androgens and behaviors in vertebrates, especially zebrafish.<\/jats:p>","DOI":"10.3390\/biology15050393","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:05:16Z","timestamp":1772211916000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavioral Alterations in Male Zebrafish After Administration of Androgen Receptor Blockers and an Activator"],"prefix":"10.3390","volume":"15","author":[{"given":"Ching-Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 840203, Taiwan"},{"name":"Division of Urology, Department of Surgery, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Audira","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-9710","authenticated-orcid":false,"given":"Ross D.","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, University of Santo Tomas, Manila 1015, Philippines"},{"name":"Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila 1015, Philippines"},{"name":"The Graduate School, University of Santo Tomas, Manila 1015, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honeymae C.","family":"Alos","sequence":"additional","affiliation":[{"name":"Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila 1015, Philippines"},{"name":"The Graduate School, University of Santo Tomas, Manila 1015, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6398-8672","authenticated-orcid":false,"given":"Chung-Der","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, Taiwan"},{"name":"Research Center for Aquatic Toxicology and Pharmacology, Chung Yuan Christian University, Taoyuan City 320314, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hsin","family":"Hung","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 840203, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","unstructured":"Handelsman, D.J. (2020). Androgen physiology, pharmacology, use and misuse. Endotext [Internet], MDText.com, Inc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1043-2760(98)00081-2","article-title":"Molecular mechanism of androgen action","volume":"9","author":"Hiipakka","year":"1998","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhou, Z.-X., Wong, C.-I., Sar, M., and Wilson, E.M. (1994). The androgen receptor: An overview. Proceedings of the 1992 Laurentian Hormone Conference, Academic Press.","DOI":"10.1016\/B978-0-12-571149-4.50017-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/1477-3163.83937","article-title":"Androgen receptor signaling in prostate cancer development and progression","volume":"10","author":"Lonergan","year":"2011","journal-title":"J. Carcinog."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0002-9440(10)65632-5","article-title":"Prostate stem cell compartments: Expression of the cell cycle inhibitor p27Kip1 in normal, hyperplastic, and neoplastic cells","volume":"153","author":"Meeker","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_6","first-page":"391","article-title":"The role of androgen in the regulation of programmed cell death\/apoptosis in normal and malignant prostatic tissue","volume":"5","author":"Isaacs","year":"1994","journal-title":"Semin. Cancer Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ijc.22365","article-title":"Androgen receptor coregulators and their involvement in the development and progression of prostate cancer","volume":"120","author":"Chmelar","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12182","DOI":"10.1073\/pnas.0804700105","article-title":"Androgen receptor is a tumor suppressor and proliferator in prostate cancer","volume":"105","author":"Niu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"26259","DOI":"10.18632\/oncotarget.8456","article-title":"Acquired resistance to the second-generation androgen receptor antagonist enzalutamide in castration-resistant prostate cancer","volume":"7","author":"Kregel","year":"2016","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJMoa1207506","article-title":"Increased survival with enzalutamide in prostate cancer after chemotherapy","volume":"367","author":"Scher","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.1168175","article-title":"Development of a second-generation antiandrogen for treatment of advanced prostate cancer","volume":"324","author":"Tran","year":"2009","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1021\/acs.chemrestox.9b00247","article-title":"Enzalutamide and apalutamide: In vitro chemical reactivity studies and activity in a mouse drug allergy model","volume":"33","author":"Ji","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1158\/0008-5472.CAN-11-3948","article-title":"ARN-509: A novel antiandrogen for prostate cancer treatment","volume":"72","author":"Clegg","year":"2012","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.eururo.2016.04.023","article-title":"Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort","volume":"70","author":"Smith","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_15","first-page":"826","article-title":"Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis","volume":"38","author":"Kumar","year":"2020","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1007\/s12272-015-0592-9","article-title":"Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats","volume":"38","author":"Kim","year":"2015","journal-title":"Arch. Pharmacal Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nicola, C., Dubois, M., Campart, C., Al Sagheer, T., Desrues, L., Schapman, D., Galas, L., Lange, M., Joly, F., and Castel, H. (2021). The prostate cancer therapy enzalutamide compared with abiraterone acetate\/prednisone impacts motivation for exploration, spatial learning and alters dopaminergic transmission in aged castrated mice. Cancers, 13.","DOI":"10.1101\/2021.04.01.438009"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14698","DOI":"10.1038\/s41598-017-14413-w","article-title":"Enzalutamide inhibits testosterone-induced growth of human prostate cancer xenografts in zebrafish and can induce bradycardia","volume":"7","author":"Melong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1089\/zeb.2012.0861","article-title":"Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond","volume":"10","author":"Kalueff","year":"2013","journal-title":"Zebrafish"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kalueff, A.V., Echevarria, D.J., and Stewart, A.M. (2014). Gaining Translational Momentum: More Zebrafish Models for Neuroscience Research, Elsevier.","DOI":"10.1016\/j.pnpbp.2014.01.022"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1038\/nprot.2010.140","article-title":"Measuring behavioral and endocrine responses to novelty stress in adult zebrafish","volume":"5","author":"Cachat","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbr.2009.01.016","article-title":"High precision liquid chromatography analysis of dopaminergic and serotoninergic responses to acute alcohol exposure in zebrafish","volume":"200","author":"Chatterjee","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124937","DOI":"10.1016\/j.chemosphere.2019.124937","article-title":"Zebrafish behavioral phenomics employed for characterizing behavioral neurotoxicity caused by silica nanoparticles","volume":"240","author":"Li","year":"2020","journal-title":"Chemosphere"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1089\/154585404774101662","article-title":"Characterization and development of courtship in zebrafish, Danio rerio","volume":"1","author":"Darrow","year":"2004","journal-title":"Zebrafish"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dutra Costa, B.P., Aquino Moura, L., Gomes Pinto, S.A., Lima-Maximino, M., and Maximino, C. (2020). Zebrafish models in neural and behavioral toxicology across the life stages. Fishes, 5.","DOI":"10.20944\/preprints201909.0234.v2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1002\/dvdy.21700","article-title":"Androgen receptor gene expression in the developing and adult zebrafish brain","volume":"237","author":"Gorelick","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1530\/REP-08-0055","article-title":"Functional characterization and expression analysis of the androgen receptor in zebrafish (Danio rerio) testis","volume":"136","author":"Wang","year":"2008","journal-title":"Reproduction"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cbpc.2009.10.001","article-title":"Zebrafish (Danio rerio) androgen receptor: Sequence homology and up-regulation by the fungicide vinclozolin","volume":"151","author":"Smolinsky","year":"2010","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25801","DOI":"10.1074\/jbc.M703268200","article-title":"Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone","volume":"282","author":"Askew","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/0018-506X(86)90004-8","article-title":"Effects of testosterone, estrogen, and dihydrotestosterone upon aggressive and sexual behavior of female rats","volume":"20","year":"1986","journal-title":"Horm. Behav."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ygcen.2013.09.019","article-title":"Current perspectives on the androgen 5 alpha-dihydrotestosterone (DHT) and 5 alpha-reductases in teleost fishes and amphibians","volume":"194","author":"Martyniuk","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_32","first-page":"e4196","article-title":"Regular care and maintenance of a zebrafish (Danio rerio) laboratory: An introduction","volume":"69","author":"Avdesh","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4055\/cios.2014.6.1.103","article-title":"How to do random allocation (randomization)","volume":"6","author":"Kim","year":"2014","journal-title":"Clin. Orthop. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Audira, G., Sampurna, B., Juniardi, S., Liang, S.-T., Lai, Y.-H., and Hsiao, C.-D. (2018). A versatile setup for measuring multiple behavior endpoints in zebrafish. Inventions, 3.","DOI":"10.3390\/inventions3040075"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"jeb182469","DOI":"10.1242\/jeb.182469","article-title":"UMATracker: An intuitive image-based tracking platform","volume":"221","author":"Yamanaka","year":"2018","journal-title":"J. Exp. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115239","DOI":"10.1016\/j.envpol.2020.115239","article-title":"Systematical exploration of the common solvent toxicity at whole organism level by behavioral phenomics in adult zebrafish","volume":"266","author":"Audira","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1006\/anbe.1996.0077","article-title":"Using randomization techniques to analyse behavioural data","volume":"51","author":"Adams","year":"1996","journal-title":"Anim. Behav."},{"key":"ref_38","unstructured":"Sullivan, L. (2020, August 28). Power and Sample Size Determination. Available online: https:\/\/sphweb.bumc.bu.edu\/otlt\/mph-modules\/bs\/bs704_power\/bs704_power_print.html."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"W566","DOI":"10.1093\/nar\/gkv468","article-title":"ClustVis: A web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap","volume":"43","author":"Metsalu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s43088-021-00117-8","article-title":"Investigating the binding affinity, molecular dynamics, and ADMET properties of 2, 3-dihydrobenzofuran derivatives as an inhibitor of fungi, bacteria, and virus protein","volume":"10","author":"Nath","year":"2021","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3758\/BF03192800","article-title":"Behavioral phenotyping in zebrafish: Comparison of three behavioral quantification methods","volume":"38","author":"Blaser","year":"2006","journal-title":"Behav. Res. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rosemberg, D.B., Rico, E.P., Mussulini, B.H.M., Piato, \u00c2.L., Calcagnotto, M.E., Bonan, C.D., Dias, R.D., Blaser, R.E., Souza, D.O., and de Oliveira, D.L. (2011). Differences in spatio-temporal behavior of zebrafish in the open tank paradigm after a short-period confinement into dark and bright environments. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019397"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Castel, H., Al Sagheer, T., Dubois, M., Campart, C., Desrues, L., Lange, M., Gandolfo, P., and Joly, F. (2019). Impact of Hormone-Therapy Used in CRPC Patients: Evaluation of Abiraterone Acetate\/Prednisone or Enzalutamide on Activity and Cognitive Functions in Aged Castrated Mice, American Society of Clinical Oncology.","DOI":"10.1200\/JCO.2019.37.15_suppl.e16526"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2013.06.033","article-title":"Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish","volume":"1527","author":"Kyzar","year":"2013","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1089\/zeb.2016.1295","article-title":"Neurochemical and behavioral responses to unpredictable chronic mild stress following developmental isolation: The zebrafish as a model for major depression","volume":"14","author":"Fulcher","year":"2017","journal-title":"Zebrafish"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"B\u00fchler, A., and Carl, M. (2021). Zebrafish tools for deciphering habenular network-linked mental disorders. Biomolecules, 11.","DOI":"10.3390\/biom11020324"},{"key":"ref_47","unstructured":"Attaran, A. (2021). Effects of Chronic Exposure to Selenium on Social Behaviour and Social Learning in Zebrafish (Danio rerio). [Ph.D. Thesis, University of Saskatchewan Saskatoon]."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e2140803","DOI":"10.1001\/jamanetworkopen.2021.40803","article-title":"Association of second-generation antiandrogens with depression among patients with prostate cancer","volume":"4","author":"Nowakowska","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s40263-022-00913-5","article-title":"Assessment and management of cognitive function in patients with prostate cancer treated with second-generation androgen receptor pathway inhibitors","volume":"36","author":"Wefel","year":"2022","journal-title":"CNS Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.applanim.2004.02.004","article-title":"Can fish suffer?: Perspectives on sentience, pain, fear and stress","volume":"86","author":"Chandroo","year":"2004","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41391-022-00541-6","article-title":"Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors\u00b1androgen deprivation therapy: A pharmacovigilance study","volume":"26","author":"Briggs","year":"2023","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/pros.21263","article-title":"Drug safety is a barrier to the discovery and development of new androgen receptor antagonists","volume":"71","author":"Foster","year":"2011","journal-title":"Prostate"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"150218","DOI":"10.1016\/j.bbrc.2024.150218","article-title":"GABAergic implications in anxiety and related disorders","volume":"724","author":"Arora","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s11055-017-0438-7","article-title":"GABA receptors in the modulation of fear memory extinction","volume":"47","author":"Dubrovina","year":"2017","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/0091-3057(94)90164-3","article-title":"Interactions between 5-hydroxytryptamine (5-HT) and testosterone in the control of sexual and nonsexual behaviour in male and female rats","volume":"47","author":"Gonzalez","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_56","first-page":"100232","article-title":"Enhancement of cognitive benefits and anxiolytic effects of scoparone (6, 7-dimethoxycoumarin) in a zebrafish (Danio rerio) model of scopolamine-induced anxiety and memory impairment","volume":"7","author":"Brinza","year":"2025","journal-title":"Pharmacol. Res.-Nat. Prod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2352","DOI":"10.7717\/peerj.2352","article-title":"Anxiolytic effects of fluoxetine and nicotine exposure on exploratory behavior in zebrafish","volume":"4","author":"Singer","year":"2016","journal-title":"PeerJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbr.2009.11.009","article-title":"Behavioral measures of anxiety in zebrafish (Danio rerio)","volume":"208","author":"Blaser","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0031-9384(74)90301-1","article-title":"A comparison of the effects of androstenedione, dihydrotestosterone and testosterone propionate on aggression in the castrated male golden hamster","volume":"13","author":"Payne","year":"1974","journal-title":"Physiol. Behav."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0018-506X(79)90042-4","article-title":"Sex-specific, behavior-specific actions of dihydrotestosterone: Activation of aggression, but not mounting in ovariectomized guinea pigs","volume":"13","author":"Goldfoot","year":"1979","journal-title":"Horm. Behav."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ygcen.2011.02.012","article-title":"5\u03b1-Dihydrotestosterone is a potent androgen in the fathead minnow (Pimephales promelas)","volume":"171","author":"Sumpter","year":"2011","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Magnhagen, C., Braithwaite, V.A., and Forsgren, E. (2008). Fish Behaviour, CRC Press.","DOI":"10.1201\/b10757"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1073\/pnas.88.13.5774","article-title":"Hormonal induction of all stages of spermatogenesis in vitro in the male Japanese eel (Anguilla japonica)","volume":"88","author":"Miura","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R1793","DOI":"10.1152\/ajpregu.1998.275.6.R1793","article-title":"Sex steroids and the initiation of puberty in male African catfish (Clarias gariepinus)","volume":"275","author":"Cavaco","year":"1998","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cbpc.2007.07.002","article-title":"Identification and characterisation of an androgen receptor from zebrafish Danio rerio","volume":"146","author":"Andersen","year":"2007","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41021-019-0140-9","article-title":"Assessing the endocrine disrupting potentials and genotoxicity in environmental samples from Taiwanese rivers","volume":"41","author":"Chou","year":"2019","journal-title":"Genes Environ."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1002\/etc.625","article-title":"Screening of multiple hormonal activities in surface water and sediment from the Pearl River system, South China, using effect-directed in vitro bioassays","volume":"30","author":"Zhao","year":"2011","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.chemosphere.2006.11.041","article-title":"Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses","volume":"67","author":"Urbatzka","year":"2007","journal-title":"Chemosphere"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"118660","DOI":"10.1016\/j.ecoenv.2025.118660","article-title":"Seasonal anti-androgen activity in the brackish Baltic waters in relation to the gene expression profiles of the blue mussel Mytilus trossulus","volume":"302","author":"Smolarz","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"158622","DOI":"10.1016\/j.scitotenv.2022.158622","article-title":"Spatial and temporal variations in anti-androgenic activity and environmental risk in a small river","volume":"853","author":"Zhou","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1111\/jfb.15322","article-title":"Behavioural responses of fishes to anthropogenic disturbances: Adaptive value and ecological consequences","volume":"103","author":"Candolin","year":"2023","journal-title":"J. Fish Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1021\/acs.estlett.5c00042","article-title":"Advancing the spatiotemporal dimension of wildlife\u2013pollution interactions","volume":"12","author":"Brand","year":"2025","journal-title":"Environ. Sci. Technol. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1023\/A:1007496528012","article-title":"Altered predator\/prey behavior in polluted environments: Implications for fish conservation","volume":"55","author":"Weis","year":"1999","journal-title":"Environ. Biol. Fishes"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1095-8649.1994.tb01085.x","article-title":"Are all prey created equal? A review and synthesis of differential predation on prey in substandard condition","volume":"45","author":"Mesa","year":"1994","journal-title":"J. Fish Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1021\/es204023d","article-title":"Environmental estrogen-induced alterations of male aggression and dominance hierarchies in fish: A mechanistic analysis","volume":"46","author":"Filby","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"117826","DOI":"10.1016\/j.watres.2021.117826","article-title":"Effects of common environmental endocrine-disrupting chemicals on zebrafish behavior","volume":"208","author":"Tao","year":"2022","journal-title":"Water Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1056\/NEJMoa1800536","article-title":"Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer","volume":"378","author":"Hussain","year":"2018","journal-title":"New Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S1470-2045(15)00518-5","article-title":"Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): A randomised, double-blind, phase 2 study","volume":"17","author":"Shore","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMoa1715546","article-title":"Apalutamide treatment and metastasis-free survival in prostate cancer","volume":"378","author":"Smith","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for metastatic, castration-sensitive prostate cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1210\/endo-103-5-1814","article-title":"Hormonal control of male reproductive behavior in the lizard, Anolis carolinensis: Role of testosterone, dihydrotestosterone, and estradiol","volume":"103","author":"Crews","year":"1978","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0018-506X(81)90012-X","article-title":"Dihydrotestosterone promotes fighting behavior of female mice","volume":"15","author":"Schechter","year":"1981","journal-title":"Horm. Behav."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0306-4530(01)00027-0","article-title":"The testosterone metabolite and neurosteroid 3\u03b1-androstanediol may mediate the effects of testosterone on conditioned place preference","volume":"26","author":"Frye","year":"2001","journal-title":"Psychoneuroendocrinology"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/5\/393\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T05:31:06Z","timestamp":1772343066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/5\/393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":84,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biology15050393"],"URL":"https:\/\/doi.org\/10.3390\/biology15050393","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}