{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:47:29Z","timestamp":1790725649949,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T00:00:00Z","timestamp":1521590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER) subtypes, ER\u03b1 and ER\u03b2, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens. Consequently, the aims of the present study were (i) to determine the absolute mRNA copy numbers of the four ER isoforms in the immune organs and cells of rainbow trout, Oncorhynchus mykiss, and to compare them to the hepatic ER numbers; (ii) to analyse the ER mRNA isoform ratios in the immune system; and, (iii) finally, to examine the alterations of immune ER mRNA expression levels in sexually immature trout exposed to 17\u03b2-estradiol (E2), as well as the alterations of immune ER mRNA expression levels in sexually mature trout during the reproductive cycle. All four ER isoforms were present in immune organs\u2014head kidney, spleen-and immune cells from head kidney and blood of rainbow trout, but their mRNA levels were substantially lower than in the liver. The ER isoform ratios were tissue- and cell-specific, both within the immune system, but also between the immune system and the liver. Short-term administration of E2 to juvenile female trout altered the ER mRNA levels in the liver, but the ERs of the immune organs and cells were not responsive. Changes of ER gene transcript numbers in immune organs and cells occurred during the reproductive cycle of mature female trout, but the changes in the immune ER profiles differed from those in the liver and gonads. The correlation between ER gene transcript numbers and serum E2 concentrations was only moderate to low. In conclusion, the low mRNA numbers of nuclear ER in the trout immune system, together with their limited estrogen-responsiveness, suggest that the known estrogen actions on trout immunity may be not primarily mediated through genomic actions, but may involve other mechanisms, such as non-genomic pathways or indirect effects.<\/jats:p>","DOI":"10.3390\/ijms19040932","type":"journal-article","created":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T05:14:55Z","timestamp":1521695695000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Immune-Specific Expression and Estrogenic Regulation of the Four Estrogen Receptor Isoforms in Female Rainbow Trout (Oncorhynchus mykiss)"],"prefix":"10.3390","volume":"19","author":[{"given":"Ayako","family":"Casanova-Nakayama","sequence":"first","affiliation":[{"name":"Centre for Fish and Wildlife Health, 3012 Bern, Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-9648","authenticated-orcid":false,"given":"Elena","family":"Wernicke von Siebenthal","sequence":"additional","affiliation":[{"name":"Centre for Fish and Wildlife Health, 3012 Bern, Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kropf","sequence":"additional","affiliation":[{"name":"Centre for Fish and Wildlife Health, 3012 Bern, Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Oldenberg","sequence":"additional","affiliation":[{"name":"Centre for Fish and Wildlife Health, 3012 Bern, Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1783-1295","authenticated-orcid":false,"given":"Helmut","family":"Segner","sequence":"additional","affiliation":[{"name":"Centre for Fish and Wildlife Health, 3012 Bern, Switzerland"},{"name":"Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36869","DOI":"10.1074\/jbc.R100029200","article-title":"The multifaceted mechanisms of estradiol and estrogen receptor signaling","volume":"276","author":"Hall","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1210\/er.2007-0001","article-title":"The complex role of estrogens in inflammation","volume":"28","author":"Straub","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.coph.2013.05.007","article-title":"Oestrogen and immunomodulation: New mechanisms that impact on peripheral and central immunity","volume":"13","author":"Nadkarni","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3389\/fimmu.2015.00635","article-title":"The immune system is a natural target for estrogen action: Opposing effects of estrogen in two prototypical autoimmune diseases","volume":"6","author":"Khan","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.0141-9838.2004.00710.x","article-title":"Hormonal and immunological mechanisms mediating sex differences in parasite infection","volume":"26","author":"Klein","year":"2004","journal-title":"Parasite Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1098\/rstb.2008.0148","article-title":"On sexual dimorphism in immune function","volume":"364","author":"Nunn","year":"2009","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12016-010-8203-5","article-title":"Estrogen receptors in immunity and autoimmunity","volume":"40","author":"Cunningham","year":"2011","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15131","DOI":"10.1073\/pnas.011513098","article-title":"Age and stage dependency of estrogen receptor expression by lymphocyte precursors","volume":"98","author":"Igarashi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.imlet.2004.10.007","article-title":"Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations","volume":"97","author":"Phiel","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1677\/JOE-06-0060","article-title":"Studies on estrogen receptor (ER) \u03b1 and \u03b2 responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists","volume":"194","author":"Stygar","year":"2007","journal-title":"J. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5716","DOI":"10.4049\/jimmunol.175.9.5716","article-title":"Estrogen receptor \u03b1 (ER\u03b1) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17\u03b2-estradiol acts through ER\u03b1 to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation","volume":"175","author":"Lambert","year":"2005","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14813","DOI":"10.1073\/pnas.0703783104","article-title":"Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER) \u03b1 and ER\u03b2 ligand treatment","volume":"104","author":"Morales","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4049\/jimmunol.180.1.630","article-title":"Selective estrogen receptor-\u03b2 agonists repress transcription of proinflammatory genes","volume":"180","author":"Cvoro","year":"2008","journal-title":"J. Immunol."},{"key":"ref_15","first-page":"369","article-title":"Gonadal steroids and immunity","volume":"17","author":"Olsen","year":"1996","journal-title":"Endocr. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: Sex-based differences predispose immune responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.2353\/ajpath.2010.090432","article-title":"17\u03b2-Estradiol inhibits wound healing in male mice via estrogen receptor-\u03b1","volume":"176","author":"Gilliver","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_18","first-page":"13","article-title":"Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone","volume":"38","author":"Beagley","year":"2003","journal-title":"Pathog. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/ajpa.21621","article-title":"The roles of the immune system in women\u2019s reproduction: Evolutionary constraints and life history trade-offs","volume":"146","author":"Abrams","year":"2011","journal-title":"Am. J. Phys. Anthropol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nri3819","article-title":"The role of sex hormones in immune protection of the female reproductive tract","volume":"15","author":"Wira","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10646-010-0588-7","article-title":"The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: A review","volume":"20","author":"Milla","year":"2011","journal-title":"Ecotoxicology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chaves-Pozo, E., Cabas, I., and Garc\u00eda-Ayala, A. (2012). Sex steroids modulate fish immune response. Sex Steroids, InTech.","DOI":"10.5772\/26844"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ygcen.2013.05.015","article-title":"Impact of environmental estrogens on fish considering the diversity of estrogen signaling","volume":"191","author":"Segner","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.marpolbul.2011.05.007","article-title":"Endocrine disrupting compounds: Can they target the immune system of fish?","volume":"63","author":"Wenger","year":"2011","journal-title":"Mar. Pollut. Bull."},{"key":"ref_25","first-page":"277","article-title":"Estrogens, estrogen receptors and their role as immunoregulators in fish","volume":"1","author":"Iwanowicz","year":"2009","journal-title":"Fish Def."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.fsi.2009.02.003","article-title":"Challenge with 17\u03b1-ethinylestradiol (EE2) during early development persistently impairs growth, differentiation, and local expression of IGF-I and IGF-II in immune organs of tilapia","volume":"26","author":"Shved","year":"2009","journal-title":"Fish Shellfish Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.dci.2010.07.007","article-title":"17\u03b2-Estradiol regulates gilthead seabream professional phagocyte responses through macrophage activation","volume":"35","author":"Liarte","year":"2011","journal-title":"Dev. Comp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.4049\/jimmunol.1301613","article-title":"Estrogen Signaling through the G Protein\u2013Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish","volume":"191","author":"Cabas","year":"2013","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cbpb.2014.06.001","article-title":"Expression of gene, protein and immunohistochemical localization of the estrogen receptor isoform ER\u03b11 in male rainbow trout lymphoid organs; indication of the role of estrogens in the regulation of immune mechanisms","volume":"174","author":"Massart","year":"2014","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ygcen.2012.09.014","article-title":"Alteration of immune function endpoints and differential expression of estrogen receptor isoforms in leukocytes from 17\u03b2-estradiol exposed rainbow trout (Oncorhynchus mykiss)","volume":"180","author":"Shelley","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.dci.2016.04.003","article-title":"A role for multiple estrogen receptors in immune regulation of common carp","volume":"66","author":"Szwejser","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/embo-reports\/kve185","article-title":"Estrogen receptors: Orchestrators of pleiotropic cellular responses","volume":"2","author":"Moggs","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Murphy, A.J., Guyre, P.M., Wira, C.R., and Pioli, P.A. (2009). Estradiol regulates expression of estrogen receptor ER\u03b146 in human macrophages. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005539"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ygcen.2010.03.013","article-title":"Mechanisms and significance of nuclear receptor auto-and cross-regulation","volume":"170","author":"Bagamasbad","year":"2011","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ygcen.2013.03.032","article-title":"Estrogen receptor function and regulation in fish and other vertebrates","volume":"192","author":"Nelson","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clbc.2016.07.015","article-title":"Mechanisms that increase stability of estrogen receptor alpha in breast cancer","volume":"17","year":"2017","journal-title":"Clin. Breast Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nrc3622","article-title":"Links between oestrogen receptor activation and proteolysis: Relevance to hormone-regulated cancer therapy","volume":"14","author":"Zhou","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/156800906775471716","article-title":"Estrogen receptor alpha: Impact of ligands on intracellular shuttling and turnover rate in breast cancer cells","volume":"6","author":"Leclercq","year":"2006","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.fsi.2014.06.021","article-title":"Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ER\u03b1 and ER\u03b22 and are functionally modulated by estrogens","volume":"40","author":"Iwanowicz","year":"2014","journal-title":"Fish Shellfish Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.gene.2006.12.030","article-title":"The complete nuclear estrogen receptor family in the rainbow trout: Discovery of the novel ER\u03b12 and both ER\u03b2 isoforms","volume":"392","author":"Nagler","year":"2007","journal-title":"Gene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.fsi.2017.07.011","article-title":"Stress differentially affects the systemic and leukocyte estrogen network in common carp","volume":"68","author":"Szwejser","year":"2017","journal-title":"Fish Shellfish Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1365-2265.2005.02420.x","article-title":"Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytes","volume":"64","author":"Stygar","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mce.2013.05.016","article-title":"Estrogen receptor \u03b1 and \u03b2 in the normal immune system and in lymphoid malignancies","volume":"375","author":"Yakimchuk","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.intimp.2006.04.019","article-title":"Effects of estrogen receptor subtype-selective agonists on immune functions in ovariectomized mice","volume":"6","author":"Li","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/cne.21240","article-title":"Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors \u03b1 and \u03b2","volume":"500","author":"Suzuki","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ygcen.2008.10.011","article-title":"Immunohistochemical detection of estrogen receptors in fish scales","volume":"160","author":"Pinto","year":"2009","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/pmic.201500261","article-title":"The \u201cbusy life\u201d of unliganded estrogen receptors","volume":"16","author":"Stellato","year":"2016","journal-title":"Proteomics"},{"key":"ref_48","unstructured":"Van den Hurk, R., and Lambert, J. (1982, January 2\u20136). Temperature and steroid effects on gonadal sex differentiation in rainbow trout. Proceedings of the International Symposium on Reproductive Physiology of Fish, Wageningen, The Netherlands."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0016-6480(90)90174-K","article-title":"Sex steroid profiles of coho salmon (Oncorhynchus kisutch) during early development and sexual differentiation","volume":"80","author":"Feist","year":"1990","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cbpa.2010.01.001","article-title":"Sex-and tissue-specific effects of waterborne estrogen on estrogen receptor subtypes and E2-mediated gene expression in the reproductive axis of goldfish","volume":"156","author":"Marlatt","year":"2010","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.yhbeh.2016.10.007","article-title":"Estrogen-dependent seasonal adaptations in the immune response of fish","volume":"88","author":"Szwejser","year":"2017","journal-title":"Horm. Behav."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1210\/mend-3-1-44","article-title":"Identification and estrogen induction of two estrogen receptors (ER) messenger ribonucleic acids in the rainbow trout liver: Sequence homology with other ERs","volume":"3","author":"Pakdel","year":"1989","journal-title":"Mol. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0008-6363(02)00505-9","article-title":"Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men: Regulation by estrogen","volume":"56","author":"Molero","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1677\/jme.0.0320975","article-title":"Analysis of the estrogen regulation of the zebrafish estrogen receptor (ER) reveals distinct effects of ER\u03b1, ER\u03b21 and ER\u03b22","volume":"32","author":"Menuet","year":"2004","journal-title":"J. Mol. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.mce.2003.12.007","article-title":"Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol","volume":"218","author":"Kroll","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1095\/biolreprod.105.039701","article-title":"Molecular characterization of estrogen receptors 1, 2a, and 2b and their tissue and ontogenic expression profiles in fathead minnow (Pimephales promelas)","volume":"73","author":"Filby","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1089\/dna.2009.0998","article-title":"Variation among Rainbow Trout (Oncorhynchus mykiss) Estrogen Receptor Isoform 3\u2032 Untranslated Regions and the Effect of 17\u03b2-Estradiol on mRNA Stability in Hepatocyte Culture","volume":"29","author":"Nagler","year":"2010","journal-title":"DNA Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mce.2007.10.013","article-title":"Auto-regulation of estrogen receptor subtypes and gene expression profiling of 17\u03b2-estradiol action in the neuroendocrine axis of male goldfish","volume":"283","author":"Marlatt","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.18047\/poljo.22.1.5","article-title":"The effect of lutein additives on biochemical parameters in blood of laying hens","volume":"22","author":"Kralik","year":"2016","journal-title":"Poljoprivreda"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chandrasekar, G., Archer, A., Gustafsson, J.-\u00c5., and Lendahl, M.A. (2010). Levels of 17\u03b2-estradiol receptors expressed in embryonic and adult zebrafish following in vivo treatment of natural or synthetic ligands. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009678"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cbpc.2011.11.006","article-title":"The effects of an in vitro exposure to 17\u03b2-estradiol and nonylphenol on rainbow trout (Oncorhynchus mykiss) peripheral blood leukocytes","volume":"155","author":"Shelley","year":"2012","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R101","DOI":"10.1186\/ar3032","article-title":"Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor \u03b1 but not estrogen receptor \u03b2","volume":"12","author":"Dulos","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.dci.2016.07.004","article-title":"The immunomodulatory role of the hypothalamus-pituitary-gonad axis: Proximate mechanism for reproduction-immune trade offs?","volume":"66","author":"Segner","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0162-3109(86)90064-0","article-title":"Estradiol-induced alteration in the immune system. II. Suppression of cellular immunity in the rat is not the result of direct estrogenic action","volume":"11","author":"Myers","year":"1986","journal-title":"Immunopharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S1567-5769(01)00045-5","article-title":"Estrogen, prolactin, and autoimmunity: Actions and interactions","volume":"1","author":"McMurray","year":"2001","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.clim.2004.05.011","article-title":"Estrogen as an immunomodulator","volume":"113","author":"Lang","year":"2004","journal-title":"Clin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/acel.12326","article-title":"How sex and age affect immune responses, susceptibility to infections, and response to vaccination","volume":"14","author":"Berger","year":"2015","journal-title":"Aging Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1002\/etc.1966","article-title":"Pathogenic infection confounds induction of the estrogenic biomarker vitellogenin in rainbow trout","volume":"31","author":"Burki","year":"2012","journal-title":"Environ. Toxicol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:56Z","timestamp":1760194676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,21]]},"references-count":68,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4]]}},"alternative-id":["ijms19040932"],"URL":"https:\/\/doi.org\/10.3390\/ijms19040932","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,21]]}}}