PMID- 36356854 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230216 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 226 DP - 2023 Feb TI - Rxrs and their partner receptor genes inducing masculinization plausibly mediated by endocrine disruption in Paralichthys olivaceus. PG - 106219 LID - S0960-0760(22)00170-4 [pii] LID - 10.1016/j.jsbmb.2022.106219 [doi] AB - Retinoid X receptors (RXRs) can form homo- or heterodimers with orphan receptors involved in multiple intertwined signaling pathways. However, there is limited study on the formation of sex phenotypes and the regulation of steroidogenesis by RXRs in fish. Here, in Paralichthys olivaceus, we first indicated that PPARgamma::RXRalpha was predictably a transcription factor for steroidogenesis genes, and Foxl2 and Dmrt1 were also transcription factors for rxrs and their partner receptor genes. When the flounder fry were exposed to LG100268 (LG, RXRs agonist, 50 mg/kg diet), the percentage of males increased from 50% to 71.4%. Before histological differentiation of the flounder ovary (3 cm TL) and testis (6 cm TL), the transcripts of rar beta and rar gamma (P < 0.05) were activated, and the steroidogenesis gene Hsd3b1 was down-regulated (P < 0.05). The ratios of testosterone (T)/17beta-estradiol (E2) were all greatly increased (P < 0.05), and the ratio of 11-ketotestosterone (11-KT)/E2 was elevated at 3 cm TL. Moreover, LG was used to treat the cultured gonads in vitro (10 muM) and the fish with intraperitoneal injection in vivo (12 mg/kg body weight), respectively. LG was able to up-regulate rxr gamma, rar gamma, and ppar delta, and Hsd3b1 was significantly up-regulated (P < 0.05). The ratios of 11-KT/E2 in the culture medium and in the ovaries of the fish were decreased. Furthermore, the recombinant flounder Foxl2 protein was able to significantly down-regulate ppar gamma (P < 0.05) and tr beta (P < 0.01) in the ovaries in vitro, and the result of the Dmrt1 in the testes was opposite to that of the Foxl2, probably indicating a feedback loop between RXRs' partner receptors and Foxl2/Dmrt1. These findings introduce for the first time the mode of action of RXRs on the flounder steroidogenesis and provide important data to learn the potential function of RXRs in fish sex differentiation and the potential role of RXRs in aquatic animals in the presence of water pollutants. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Zou, Congcong AU - Zou C AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. FAU - Wang, Lijuan AU - Wang L AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. FAU - Shu, Chang AU - Shu C AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. FAU - Tan, Xungang AU - Tan X AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. FAU - Wu, Zhihao AU - Wu Z AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. FAU - Zou, Yuxia AU - Zou Y AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. FAU - Li, Ze AU - Li Z AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. FAU - Wang, Guoyu AU - Wang G AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. FAU - Song, Zongcheng AU - Song Z AD - Shenghang Aquatic Science and Technology Co. Ltd., Weihai 264200, PR China. FAU - You, Feng AU - You F AD - CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China. Electronic address: youfeng@qdio.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221108 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Retinoid X Receptors) SB - IM MH - Male MH - Animals MH - Female MH - Retinoid X Receptors/genetics MH - *Flounder/genetics MH - Gene Expression Regulation, Developmental MH - Gonads/metabolism MH - Ovary/metabolism OTO - NOTNLM OT - Flounder OT - Gonad OT - LG100268 OT - Retinoid X receptors OT - Sex differentiation OT - Steroidogenesis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/11/11 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/11/10 19:27 PHST- 2022/08/19 00:00 [received] PHST- 2022/11/03 00:00 [revised] PHST- 2022/11/06 00:00 [accepted] PHST- 2022/11/11 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/11/10 19:27 [entrez] AID - S0960-0760(22)00170-4 [pii] AID - 10.1016/j.jsbmb.2022.106219 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2023 Feb;226:106219. doi: 10.1016/j.jsbmb.2022.106219. Epub 2022 Nov 8.