赵砚彬;胡建英;

• 1:北京大学城市与环境学院

摘要(Abstract)：

孕激素和糖皮质激素的环境行为和生态毒理效应是即环境雌激素和雄激素之后近年来国内外环境激素研究的又一热点课题。由于广泛应用于临床医疗等,这两类物质通过污水处理厂不完全处理和人类农业或畜牧业活动的直接排放从而进入水体环境,进而对生态系统和人类健康产生潜在危害。环境监测数据显示,在地表水中,多种物质存在ng·L-1浓度水平;在污水处理厂进出水中,浓度水平更高,甚至达到数百ng·L-1。孕激素和糖皮质激素类物质主要通过激素受体途径发挥毒性效应,如孕激素受体(PR),糖皮质激素受体(GR)和盐皮质激素受体(MR)。对水生脊椎动物的内分泌系统干扰作用是目前研究的焦点。这两类物质能够影响脑垂体性腺轴转录水平和相应激素合成,影响性腺发育以及导致繁殖能力损伤。这一毒性效应甚至发生在环境浓度水平之下。除此之外,随着组学技术的广泛应用,更多的潜在毒性终点不断被发掘,如对昼夜节律系统和免疫应答的干扰作用。这些研究引导着对环境孕激素和糖皮质激素生态毒理学效应更加深入的理解。

关键词(KeyWords)： 孕激素;糖皮质激素;环境行为;生态毒理效应;内分泌干扰;昼夜节律;免疫反应

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(No.41330637)

作者(Author): 赵砚彬;胡建英;

Email:

DOI:

参考文献(References)：

• [1]United Nations Environment Programme and the World Health Organization.State of the Science of Endocrine Disrupting Chemicals 2012[R].WHO/UNEP,2013
• [2]Liu J L,Wong M H.Pharmaceuticals and personal care products(PPCPs):A review on environmental contamination in China[J].Environment International,2013,59:208-224
• [3]Chang H,Wan Y,Hu J Y.Determination and source apportionment of five classes of steroid hormones in urban rivers[J].Environmental Science&Technology,2009,43(20):7691-7698
• [4]Fent K,Weston A A,Caminada D.Ecotoxicology of human pharmaceuticals[J].Environmental Science&Technology,2006,76(2):122-159
• [5]Nash J P,Kime D E,Van der Ven L T,et al.Long-term exposure to environmental concentrations of the pharmaceutical ethynylestradiol causes reproductive failure in fish[J].Environmental Health Perspectives,2004,112(17):1725-1733
• [6]Vajda A M,Barber L B,Gray J L,et al.Reproductive disruption in fish downstream from an estrogenic wastewater effluent[J].Environmental Science&Technology,2008,42(9):3407-3414
• [7]Mil a S,Depiereux S,Kestemont P.The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish:A review[J].Ecotoxicology,2011,20(2):305-319
• [8]Sitruk-Ware R.Pharmacological profile of progestins[J].Maturitas,2004,47(4):277-283
• [9]van der Laan S,Meijer O C.Pharmacology of glucocorticoids:Beyond receptors[J].European Journal of Pharmacology,2008,585(2-3):483-491
• [10]Kumar V,Johnson A C,Trubiroha A,et al.The challenge presented by progestins in ecotoxicological research:A critical review[J].Environmental Science&Technology,2015,49(5):2625-2638
• [11]Fent K.Progestins as endocrine disrupters in aquatic ecosystems:Concentrations,effects and risk assessment[J].Environment International,2015,84:115-130
• [12]Kugathas S,Wil iams R J,Sumpter J P.Prediction of environmental concentrations of glucocorticoids:the River Thames,UK,as an example[J].Environment International,2012,40:15-23
• [13]Mil a S,Wang N,Mandiki S N,et al.Corticosteroids:Friends or foes of teleost fish reproduction?[J].Comparative Biochemistry and Physiology Part A:Molecular&Integrative Physiology,2009,153(3):242-251
• [14]国家环境保护总局.2000年中国环境状况公报[R].北京:中国环境保护总局,2000State Environmental Protection Administration.State of the Environment Report in China,2000[R].Beijing:State Environmental Protection Administration of China,2000(in Chinese)
• [15]中国环境科学研究院.《畜禽养殖业水污染物排放标准》(征求意见稿)编制说明[R].北京:中国环境科学研究院,2011Chinese Research Academy of Environmental Sciences.Discharge Standard of Pollutants for Livestock and Poultry Breeding(Draft Standards for Comment)Description for Drawing up[R].Beijing:Chinese Research Academy of Environmental Sciences,2011(in Chinese)
• [16]Liu S,Ying G G,Zhang R Q,et al.Fate and occurrence of steroids in swine and dairy cattle farms with different farming scales and wastes disposal systems[J].Environmental Pollution,2012,170:190-201
• [17]Besse J P,Garric J.Progestagens for human use,exposure and hazard assessment for the aquatic environment[J].Environmental Pollution,2009,157(12):3485-3494
• [18]Runnal s T J,Margiotta-Casalucia L,Kugathasa S.Pharmaceuticals in the aquatic environment:Steroids and anti-steroids as high priorities for research[J].Human and Ecological Risk Assessment,2010,16:1318-1338
• [19]Fernandez M P,Ikonomou M G,Buchanan I.An assessment of estrogenic organic contaminants in Canadian wastewaters[J].Science of the Total Environment,2007,373(1):250-269
• [20]Pauwels B,Noppe H,De Brabander H,et al.Comparison of steroid hormone concentrations in domestic and hospital wastewater treatment plants[J].Journal of Environmental Engineering,2008,134(11):933-936
• [21]Chang H,Wan Y,Wu S,et al.Occurrence of androgens and progestogens in wastewater treatment plants and receiving river waters:Comparison to estrogens[J].Water Research,2011,45(2):732-740
• [22]Liu S,Ying G G,Zhao J L,et al.Trace analysis of 28steroids in surface water,wastewater and sludge samples by rapid resolution liquid chromatography-electrospray ionization tandem mass spectrometry[J].Journal of Chromatography A,2011,1218(10):1367-1378
• [23]Liu S S,Ying G G,Liu S,et al.Analysis of 21 progestagens in various matrices by ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLCMS/MS)with diverse sample pretreatment[J].Analytical and Bioanalytical Chemistry,2014,406(28):7299-7311
• [24]Piram A,Salvador A,Gauvrit J Y,et al.Development and optimisation of a single extraction procedure for the LC/MS/MS analysis of two pharmaceutical classes residues in sewage treatment plant[J].Talanta,2008,74(5):1463-1475
• [25]Chang H,Hu J,Shao B.Occurrence of natural and synthetic glucocorticoids in sewage treatment plants and receiving river waters[J].Environmental Science&Technology,2007,41(10):3462-3468
• [26]Fan Z,Wu S,Chang H,et al.Behaviors of glucocorticoids,androgens and progestogens in a municipal sewage treatment plant:Comparison to estrogens[J].Environmental Science&Technology,2011,45(7):2725-2733
• [27]Vul iet E,Baugros J B,Flament-Waton M M,et al.Analytical methods for the determination of selected steroid sex hormones and corticosteriods in wastewater[J].Analytical and Bioanalytical Chemistry,2007,387(6):2143-2151
• [28]Al-Odaini N A,Zakaria M P,Yaziz M I,et al.Multi-residue analytical method for human pharmaceuticals and synthetic hormones in river water and sewage effluents by solid phase extraction and liquid chromatography-tandem mass spectrometry[J].Journal of Chromatography A,2010,1217(44):6791-6806
• [29]Vul iet E,Cren-OlivéC.Screening of pharmaceuticals and hormones at the regional scale,in surface and groundwaters intended to human consumption[J].Environmental Pollution,2011,159(10):2929-2934
• [30]Velicu M,Suri R.Presence of steroid hormones and antibiotics in surface water of agricultural,suburban and mixed-use areas[J].Environmental Monitoring and Assessment,2009,154(1-4):349-359
• [31]Ammann A A,Macikova P,Groh K J.et al.LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters[J].Analytical and Bioanalytical Chemistry,2014,406(29):7653-7665
• [32]Zeilinger J,Steger-Hartmann T,Maser E,et al.Effects of synthetic gestagens on fish reproduction[J].Environmental Toxicology and Chemistry,2009,28(12):2663-2670
• [33]Runnal s T J,Beresford N,Losty E,et al.Several synthetic progestins with different potencies adversely affect reproduction of fish[J].Environmental Science&Technology,2013,47(4):2077-2084
• [34]Paulos P,Runnal s T J,Nal ani G,et al.Reproductive responses in fathead minnow and Japanese medaka following exposure to a synthetic progestin,norethindrone[J].Aquatic Toxicology,2010,99(2):256-262
• [35]Zhao Y B,Castiglioni S,Fent K.Synthetic progestins medroxyprogesterone acetate anddydrogesterone and their binary mixtures adversely affect reproduction and lead to histological and transcriptional alterations in zebrafish(Danio rerio)[J].Environmental Science&Technology,2015,49(7):4636-4645
• [36]Zhao Y B,Castiglioni S,Fent K.Environmental progestins progesterone and drospirenone alter the circadian rhythm network inzebrafish(Danio rerio)[J].Environmental Science&Technology,2015,49(16):10155-10164
• [37]Han J,Wang Q,Wang X,et al.The synthetic progestin megestrol acetate adversely affects zebrafish reproduction[J].Aquatic Toxicology,2014,150:66-72
• [38]Overturf M D,Overturf C L,Carty D R,et al.Levonorgestrel exposure to fathead minnows(Pimephales promelas)alters survival,growth,steroidogenic gene expression and hormone production[J].Aquatic Toxicology,2014,148:152-161
• [39]Kroupova H K,Trubiroha A,Lorenz C,et al.The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach(Rutilus rutilus)[J].Aquatic Toxicology,2014,154:154-162
• [40]Sharpe R L,Mac Latchy D L,Courtenay S C,et al.Effects of a model androgen(methyl testosterone)and a model anti-androgen(cyproterone acetate)on reproductive endocrine endpoints in a short-term adult mummichog(Fundulus heteroclitus)bioassay[J].Aquatic Toxicology,2004,67(3):203-215
• [41]La Lone C A,Vil eneuve D L,Olmstead A W,et al.Effects of a glucocorticoid receptor agonist,dexamethasone,on fathead minnow reproduction,growth,and development[J].Environmental Toxicology and Chemistry,2012,31(3):611-622
• [42]Consten D,Lambert J G,Komen H,et al.Corticosteroids affect the testicular androgen production in male common carp(Cyprinus carpio L.)[J].Biology of Reproduction,2002,66(1):106-111
• [43]Guiloski I C,Ribas J L,Pereira Lda S,et al.Effects of trophic exposure to dexamethasone and diclofenac in freshwater fish[J].Ecotoxicology and Environmental Safety,2015,114:204-211
• [44]Shankar D S,Kulkarni R S.Effect of cortisol on testis of freshwater fish Notopterus notopterus(Pallas)[J].Indian Journal of Experimental Biology,2000,38(12):1227-1230
• [45]Kugathas S,Runnal s T J,Sumpter J P.Metabolic and reproductive effects of relatively low concentrations of beclomethasone dipropionate,a synthetic glucocorticoid,on fathead minnows[J].Environmental Science&Technology,2013,47(16):9487-9495
• [46]Levavi-Sivan B,Bogerd J,Maanós E L,et al.Perspectives on fish gonadotropins and their receptors[J].General and Comparative Endocrinology,2010,165(3):412-437
• [47]Zucchi S,Mirbahai L,Castiglioni S,et al.Transcriptional and physiological responses induced by binary mixtures of drospirenone and progesterone in zebrafish(Danio rerio)at environmental concentrations[J].Environmental Science&Technology,2014,48(6):3523-3531
• [48]Menuet A,Pellegrini E,Brion F,et al.Expression and estrogen-dependent regulation of the zebrafish brain aromatase gene[J].Journal of Comparative Neurology,2005,485(4):304-320
• [49]Blüthgen N,Sumpter J P,Odermatt A,et al.Effects of low concentrations of the antiprogestin mifepristone(RU486)in adults and embryos of zebrafish(Danio rerio):2.Gene expression analysis and in vitro activity[J].Aquatic Toxicology,2013,144-145:96-104
• [50]Liang Y Q,Huang G Y,Ying G G,et al.The effects of progesterone on transcriptional expression profiles of genes associated with hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes during the early development of zebrafish(Danio rerio)[J].Chemosphere,2015,128:199-206
• [51]Ozaki Y,Higuchi M,Miura C,et al.Roles of 11betahydroxysteroid dehydrogenase in fish spermatogenesis[J].Endocrinology,2006,147(11):5139-5146
• [52]杨丽华,张小艳,李伟,等.氢化可的松对雄性稀有鮈鲫肾上腺激素调节功能基因的干扰作用[J].环境科学学报,2009(4):802-807Yang L H,Zhang X Y,Li W,et al.Roles of cortisol exposure on functional genes in the HPA axis in male Chinese rare minnow(Grobiocypris rarus)[J].Acta Scientiae Circumstantiae,2009(4):802-807(in Chinese)
• [53]Schiller V,Wichmann A,Kriehuber R,et al.Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption[J].Reproductive Toxicology,2013,42:210-223
• [54]Zhao Y,Wang C,Xia S,et al.Biosensor medaka for monitoring intersex caused by estrogenic chemicals[J].Environmental Science&Technology,2014,48(4):2413-2420
• [55]Parrott J L,Blunt B R.Life-cycle exposure of fathead minnows(Pimephales promelas)to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males[J].Environmental Toxicology,2005,20(2):131-141
• [56]Fenske M,Segner H.Aromatase modulation alters gonadal differentiation in developing zebrafish(Danio rerio)[J].Aquatic Toxicology,2004,67(2):105-126
• [57]Morthorst J E,Holbech H,Bjerregaard P.Trenbolone causes irreversible masculinization of zebrafish at environmental y relevant concentrations[J].Aquatic Toxicology,2010,98(4):336-343
• [58]Zucchi S,Castiglioni S,Fent K.Progestins and antiprogestins affect gene expression in early development in zebrafish(Danio rerio)at environmental concentrations[J].Environmental Science&Technology,2012,46(9):5183-5192
• [59]Liang Y Q,Huang G Y,Ying G G,et al.Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic-pituitary-thyroid axis in zebrafish embryos-larvae[J].Comparative Biochemistry and Physiology Part C:Toxicology&Pharmacology,2015,167:101-107
• [60]Overturf M D,Huggett D B.Responses to various exposure durations of levonorgestrel during early-life stages of fathead minnows(Pimephales promelas)[J].AquaticToxicology,2015,161:33-40
• [61]Hil egass J M,Vil ano C M,Cooper K R,et al.Glucocorticoids alter craniofacial development and increase expression and activity of matrix metal oproteinases in developing zebrafish(Danio rerio)[J].Toxicological Sciences,2008,102(2):413-424
• [62]La Lone C A,Vil eneuve D L,Olmstead A W,et al.Effects of a glucocorticoid receptor agonist,dexamethasone,on fathead minnow reproduction,growth,and development[J].Environmental Toxicology and Chemistry,2012,31(3):611-622
• [63]Liang Y Q,Huang G Y,Liu S S,et al.Long-term exposure to environmentally relevant concentrations of progesterone and norgestrel affects sex differentiation in zebrafish(Danio rerio)[J].Aquatic Toxicology,2015,160:172-179
• [64]Zucchi S,Castiglioni S,Fent K.Progesterone alters global transcription profiles at environmental concentrations in brain and ovary of female zebrafish(Danio rerio)[J].Environmental Science&Technology,2013,47(21):12548-12556
• [65]Mc Kay L I,Cidlowski J A.Molecular control of immune/inflammatory responses:Interactions between nuclear factor-kappa B and steroid receptor-signaling pathways[J].Endocrine Reviews,1999,20(4):435-459
• [66]Buttgereit F,Scheffold A.Rapid glucocorticoid effects on immune cells[J].Steroids,2002,67(6):529-534
• [67]Pietsch C,Neumann N,Knopf K,et al.Progestogens cause immunosuppression of stimulated carp(Cyprinus carpio L.)leukocytes in vitro[J].Comparative Biochemistry and Physiology Part C:Toxicology&Pharmacology,2009,150(1):16-24
• [68]Pietsch C,Neumann N,Preuer T,et al.In vivo treatment with progestogens causes immunosuppression of carp Cyprinus carpio leucocytes by affecting nitric oxide production and arginase activity[J].Journal of Fish Biology,2011,79(1):53-69
• [69]Huang W C,Yang C C,Chen I H,et al.Treatment of glucocorticoids inhibited early immune responses and impaired cardiac repair in adult zebrafish[J].PLo S One,2013,8(6):e66613
• [70]刘小玲,葛海燕,田珍,等.皮质醇对黄颡鱼头肾巨噬细胞呼吸爆发活动的影响[J].华中农业大学学报,2008,27(6):749-754Liu X L,Ge H Y,Tian Z,et al.Effects of cortisol on respiratory burst of head kidney macrophages in Pelteobagrus fulvidraco[J].Journal of Huazhong Agricultural University,2008,27(6):749-754(in Chinese)
• [71]葛海燕,刘小玲,罗贤奎,等.皮质醇混饲投喂对黄颡鱼幼鱼生长及外周血细胞的影响[J].淡水渔业,2007(1):43-47Ge H Y,Liu X L,Luo X K,et al.The effects of dietary intake of cortisol on the growth and circulating blood cells in fingerling yel ow catfish(Pelteobagrus fulvidraco)[J].Freshwater Fisheries,2007(1):43-47(in Chinese)