title: The secretion, synthesis, and metabolism of cortisol and its downstream genes in the H-P-I axis of rare minnows (Gobiocypris rarus) are disrupted by acute waterborne cadmium exposure.
abstract: The H (hypothalamic)-P (pituitary)-I (interrenal) axis plays a critical role in the fish stress response and is regulated by several factors. Cadmium (Cd) is one of the most toxic heavy metals in the world, but its effects on the H-P-I axis of teleosts are largely unknown. Using rare minnow (Gobiocypris rarus) as an experimental animal, we found that Cd only disrupted the secretion and synthesis of cortisol. Neither hormones at the H or P level nor the expressions of their receptor genes (corticotropin-releasing hormone receptor (CRHR) and melanocortin receptor 2 (MC2R)) were affected. Steroidogenic acute regulator (StAR), CYP11A1 and CYP11B1, which encode the key enzymes in the cortisol synthesis pathway, were significantly up-regulated in the kidney (including the head kidney). The level of 11β-HSD2, which is required for the conversion of cortisol to cortisone, was increased in the kidney, intestine, brain, and hepatopancreas, whereas the expression of 11β-HSD1, which encodes the reverse conversion enzyme, was increased in the gill, kidney and almost unchanged in other tissues. The enzyme activity concentration of 11β-HSD2 was increased in the kidney as well. The level of glucocorticoid receptor (GR) decreased in the intestine, gill and muscle, and the key GR regulator FK506 binding protein5 (FKBP5) was up-regulated in the GR-decreased tissues, whereas the level of nuclear receptor co-repressor 1 (NCoR1), another GR regulator remained almost unchanged. Thus, GR, FKBP5 and 11β-HSD2 may be involved in Cd-induced cortisol disruption.
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University School of Life Science, Chongqing 400715, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Conservation and Utilization of Fishes Resources in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, Neijiang Normal University, School of Life Science, Neijiang 641000, China.
authors.forename: Bi-Wen
authors.initials: BW
authors.lastname: Xie
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University School of Life Science, Chongqing 400715, China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University School of Life Science, Chongqing 400715, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University School of Life Science, Chongqing 400715, China. Electronic address: zhangyg@swu.edu.cn.
authors.forename: Yao-Guang
authors.initials: YG
authors.lastname: Zhang
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D003530:Cyprinidae / Q000235:genetics / Q000378:metabolism*; D052244:Endocrine Disruptors / Q000633:toxicity*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005880:Gills / Q000187:drug effects / Q000378:metabolism; D006854:Hydrocortisone / Q000096:biosynthesis / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D052244:Endocrine Disruptors; D029941:Fish Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014874:Water Pollutants, Chemical; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D022021:Tacrolimus Binding Proteins; D019256:Cadmium Chloride; D006854:Hydrocortisone
keywords: 11β−HSD2; Cadmium; Cortisol secretion and synthesis; FKBP5; Glucocorticoid receptor; H–P–I axis