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Journal of Endocrinological Investigation

Open Access 18-04-2024 | Short Review

Endocrine disruptors, aryl hydrocarbon receptor and cortisol secretion

Authors: F. Pecori Giraldi, F. Ferraù, M. Ragonese, S. Cannavò

Published in: Journal of Endocrinological Investigation

Abstract

Purpose

Endocrine disruptors exert a plethora of effects in endocrine tissues, from altered function to carcinogenesis. Given its lipophilic nature, the adrenal cortex represents an ideal target for endocrine disruptors and thus, possibly, xenobiotic-induced adrenocortical dysfunction. However, there is no clear understanding of the effect of endocrine disruptors on adrenal steroidogenesis, in particular as regards the aryl hydrocarbon receptor (AHR) pathway, one of the key mediators.

Methods

The present review recapitulates available evidence on the effects of AHR ligands on adrenal steroidogenesis, with focus on cortisol secretion.

Results

Short-term exposure to AHR ligands most often induced a stress-like corticosteroid response followed by decreased responsiveness to stressors with long-term exposure. This was observed in several experimental models across species as well as in animals and humans in real-life settings. Prenatal exposure led to different effects according to sex of the offspring, as observed in murine models and in children from mothers in several countries. In vitro findings proved highly dependent on the experimental setting, with reduced cortisol response and steroidogenic enzyme synthesis mostly observed in fish and increased cortisol synthesis and secretion observed in murine and human adrenal cell lines. Of note, no AHR-binding element was detected in steroidogenic enzyme promoters, suggesting the involvement of additional factors.

Conclusion

Our review provides evidence for the impact of AHR ligands on adrenocortical function and indicates further avenues of research to better clarify its effects.

Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y (1999) Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13:20–25. https://doi.org/10.1101/gad.13.1.20CrossRefPubMedPubMedCentral

Johnson-Restrepo B, Kannan K, Rapaport DP, Rodan BD (2005) Polybrominated diphenyl ethers and polychlorinated biphenyls in human adipose tissue from New York. Environ Sci Technol 39:5177–5182. https://doi.org/10.1021/es050399xCrossRefPubMed

Hornsby PJ (1989) Steroid and xenobiotic effects on the adrenal cortex: mediation by oxidative and other mechanisms. Free Radic Biol Med 6:103–115. https://doi.org/10.1016/0891-5849(89)90163-9CrossRefPubMed

Elbekai RH, El-Kadi AO (2004) Modulation of aryl hydrocarbon receptor-regulated gene expression by arsenite, cadmium, and chromium. Toxicology 202:249–269. https://doi.org/10.1016/j.tox.2004.05.009CrossRefPubMed

Amara IE, Anwar-Mohamed A, Abdelhamid G, El-Kadi AO (2012) Effect of mercury on aryl hydrocarbon receptor-regulated genes in the extrahepatic tissues of C57BL/6 mice. Food Chem Toxicol 50:2325–2334. https://doi.org/10.1016/j.fct.2012.04.028CrossRefPubMed

Bonefeld-Jørgensen EC, Long M, Hofmeister MV, Vinggaard AM (2007) Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review. Environ Health Perspect 115(Suppl 1):69–76. https://doi.org/10.1289/ehp.9368CrossRefPubMedPubMedCentral

Han EH, Kim HG, Lee EJ, Jeong HG (2015) Endosulfan induces CYP1A1 expression mediated through aryl hydrocarbon receptor signal transduction by protein kinase C. Toxicol Res 31:339–345. https://doi.org/10.5487/TR.2015.31.4.339CrossRefPubMedPubMedCentral

Halwachs S, Wassermann L, Lindner S, Zizzadoro C, Honscha W (2013) Fungicide prochloraz and environmental pollutant dioxin induce the ABCG2 transporter in bovine mammary epithelial cells by the arylhydrocarbon receptor signaling pathway. Toxicol Sci 131:491–501. https://doi.org/10.1093/toxsci/kfs304CrossRefPubMed

Korashy HM, Shayeganpour A, Brocks DR, El-Kadi AO (2007) Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci 97:32–43. https://doi.org/10.1093/toxsci/kfm012CrossRefPubMed

10.

Bestervelt LL, Pitt JA, Nolan CJ, Piper WN (1993) TCDD alters pituitary-adrenal function. II: evidence for decreased bioactivity of ACTH. Neurotoxicol Teratol 15:371–376. https://doi.org/10.1016/0892-0362(93)90053-qCrossRefPubMed

11.

DiBartolomeis MJ, Moore RW, Peterson RE, Jefcoate CR (1986) Hypercholesterolemia and the regulation of adrenal steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats. Toxicol Appl Pharmacol 85:313–323. https://doi.org/10.1016/0041-008x(86)90338-8CrossRefPubMed

12.

Mebus CA, Piper WN (1986) Decreased rat adrenal 21-hydroxylase activity associated with decreased adrenal microsomal cytochrome P-450 after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Pharmacol 35:4359–4362. https://doi.org/10.1016/0006-2952(86)90748-3CrossRefPubMed

13.

Sanderson JT (2006) The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci 94:3–21. https://doi.org/10.1093/toxsci/kfl051CrossRefPubMed

14.

Foster WG, Mertineit C, Yagminas A, McMahon A, Lecavalier P (1995) The effects of hexachlorobenzene on circulating levels of adrenal steroids in the ovariectomized rat. J Biochem Toxicol 10:129–135. https://doi.org/10.1002/jbt.2570100303CrossRefPubMed

15.

Malendowicz LK, Trejter M, Rebuffat P, Ziolkowska A, Nussdorfer GG, Majchrzak M (2006) Effects of some endocrine disruptors on the secretory and proliferative activity of the regenerating rat adrenal cortex. Int J Mol Med 18:197–200 (PMID: 16786173)PubMed

16.

Ahmad S, Sharma S, Afjal MA, Habib H, Akhter J, Goswami P, Parvez S, Akhtar M, Raisuddin S (2022) mRNA expression and protein-protein interaction (PPI) network analysis of adrenal steroidogenesis in response to exposure to phthalates in rats. Environ Toxicol Pharmacol 89:103780. https://doi.org/10.1016/j.etap.2021.103780CrossRefPubMed

17.

Lelli SM, Ceballos NR, Mazzetti MB, Aldonatti CA, Martín S, de Viale LC (2007) Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis. Biochem Pharmacol 73:873–879. https://doi.org/10.1016/j.bcp.2006.11.012CrossRefPubMed

18.

Chen X, Mo J, Zhang S, Li X, Huang T, Zhu Q, Wang S, Chen X, Ge RS (2019) 4-Bromodiphenyl ether causes adrenal gland dysfunction in rats during puberty. Chem Res Toxicol 32:1772–1779. https://doi.org/10.1021/acs.chemrestox.9b00123CrossRefPubMed

19.

Dungar BM, Schupbach CD, Jacobson JR, Kopf PG (2021) Adrenal corticosteroid perturbation by the endocrine disruptor BDE-47 in a human adrenocortical cell line and male rats. Endocrinology 162:bqab160. https://doi.org/10.1210/endocr/bqab160CrossRefPubMedPubMedCentral

20.

Sobolewski M, Conrad K, Marvin E, Allen JL, Cory-Slechta DA (2018) Endocrine active metals, prenatal stress and enhanced neurobehavioral disruption. Horm Behav 101:36–49. https://doi.org/10.1016/j.yhbeh.2018.01.004CrossRefPubMedPubMedCentral

21.

Chang LL, Wun WS, Wang PS (2012) In utero and neonate exposure to nonylphenol develops hyperadrenalism and metabolic syndrome later in life. I. first generation rats (F1). Toxicology 301:40–49. https://doi.org/10.1016/j.tox.2012.06.017CrossRefPubMed

22.

Panagiotidou E, Zerva S, Mitsiou DJ, Alexis MN, Kitraki E (2014) Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats. J Endocrinol 220:207–218. https://doi.org/10.1530/JOE-13-0416CrossRefPubMed

23.

Yaglova NV, Tsomartova DA, Yaglov VV (2017) Differences in adrenal steroid hormones production in pubertal rats exposed to low doses of endocrine disruptor DDT during prenatal and postnatal development. Biomed Khim 63:306–311. https://doi.org/10.18097/PBMC20176304306CrossRefPubMed

24.

Desaulniers D, Xiao GH, Cummings-Lorbetskie C (2013) Effects of lactational and/or in utero exposure to environmental contaminants on the glucocorticoid stress-response and DNA methylation of the glucocorticoid receptor promoter in male rats. Toxicology 308:20–33. https://doi.org/10.1016/j.tox.2013.03.006CrossRefPubMed

25.

Lan HC, Lin IW, Yang ZJ, Lin JH (2015) Low-dose bisphenol A activates Cyp11a1 gene expression and corticosterone secretion in adrenal gland via the JNK signaling pathway. Toxicol Sci 148:26–34. https://doi.org/10.1093/toxsci/kfv162CrossRefPubMed

26.

Ziolkowska A, Belloni AS, Nussdorfer GG, Nowak M, Malendowicz LK (2006) Endocrine disruptors and rat adrenocortical function: studies on freshly dispersed and cultured cells. Int J Mol Med 18:1165–1168PubMed

27.

Murray IA, Patterson AD, Perdew GH (2014) Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer 14:801–814. https://doi.org/10.1038/nrc3846CrossRefPubMedPubMedCentral

28.

Abbott BD, Probst MR (1995) Developmental expression of two members of a new class of transcription factors: II. expression of aryl hydrocarbon receptor nuclear translocator in the C57BL/6N mouse embryo. Dev Dyn 204:144–155. https://doi.org/10.1002/aja.1002040205CrossRefPubMed

29.

Abbott BD, Birnbaum LS, Perdew GH (1995) Developmental expression of two members of a new class of transcription factors: I. expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo. Dev Dyn 204:133–143. https://doi.org/10.1002/aja.1002040204CrossRefPubMed

30.

Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SS, Kimura S, Nebert DW, Rudikoff S, Ward JM, Gonzalez FJ (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268:722–726. https://doi.org/10.1126/science.7732381CrossRefPubMed

31.

Sun N, Wang H, Wang XY, Yu Q, Han JY, Huang Y, Zhou WX (2023) Deletion of AhR attenuates fear memory leaving other types of memory intact. Behav Brain Res 451:114505. https://doi.org/10.1016/j.bbr.2023.114505CrossRefPubMed

32.

Leliavski A, Shostak A, Husse J, Oster H (2014) Impaired glucocorticoid production and response to stress in Arntl-deficient male mice. Endocrinology 155:133–142. https://doi.org/10.1210/en.2013-1531CrossRefPubMed

33.

Oster H, Challet E, Ott V, Arvat E, de Kloet ER, Dijk DJ, Lightman S, Vgontzas A, Van Cauter E (2017) The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids. Endocr Rev 38:3–45. https://doi.org/10.1210/er.2015-1080CrossRefPubMed

34.

Thang NQ, Huy BT, Van Tan L, Phuong NTK (2017) Lead and arsenic accumulation and its effects on plasma cortisol levels in Oreochromis sp. Bull Environ Contam Toxicol 99:187–193. https://doi.org/10.1007/s00128-017-2113-7CrossRefPubMed

35.

Kirubagaran R, Joy KP (1991) Changes in adrenocortical-pituitary activity in the catfish, Clarias batrachus (L.), after mercury treatment. Ecotoxicol Environ Saf 22:36–44. https://doi.org/10.1016/0147-6513(91)90045-qCrossRefPubMed

36.

Kennedy CJ, Farrell AP (2005) Ion homeostasis and interrenal stress responses in juvenile Pacific herring, Clupea pallasi, exposed to the water-soluble fraction of crude oil. J Exp Mar Biol Ecol 323:43–56. https://doi.org/10.1016/j.jembe.2005.02.021CrossRef

37.

Quabius ES, Balm PH, Wendelaar Bonga SE (1997) Interrenal stress responsiveness of tilapia (Oreochromis mossambicus) is impaired by dietary exposure to PCB 126. Gen Comp Endocrinol 108:472–482. https://doi.org/10.1006/gcen.1997.7003CrossRefPubMed

38.

Reddam A, Mager EM, Grosell M, McDonald MD (2017) The impact of acute PAH exposure on the toadfish glucocorticoid stress response. Aquat Toxicol 192:89–96. https://doi.org/10.1016/j.aquatox.2017.08.014CrossRefPubMed

39.

Aluru N, Vijayan MM (2006) Aryl hydrocarbon receptor activation impairs cortisol response to stress in rainbow trout by disrupting the rate-limiting steps in steroidogenesis. Endocrinology 147:1895–1903. https://doi.org/10.1210/en.2005-1143CrossRefPubMed

40.

Wilson JM, Vijayan MM, Kennedy CJ, Iwama GK, Moon TW (1998) ß-Naphthoflavone abolishes interrenal sensitivity to ACTH stimulation in rainbow trout. J Endocrinol 157:63–70. https://doi.org/10.1677/joe.0.1570063CrossRefPubMed

41.

Gesto M, Soengas JL, Míguez JM (2008) Acute and prolonged stress responses of brain monoaminergic activity and plasma cortisol levels in rainbow trout are modified by PAHs (naphthalene, ß-naphthoflavone and benzo(a)pyrene) treatment. Aquat Toxicol 86:341–351. https://doi.org/10.1016/j.aquatox.2007.11.014CrossRefPubMed

42.

Leblond VS, Bisson M, Hontela A (2001) Inhibition of cortisol secretion in dispersed head kidney cells of rainbow trout (Oncorhynchus mykiss) by endosulfan, an organochlorine pesticide. Gen Comp Endocrinol 121:48–56. https://doi.org/10.1006/gcen.2000.7556CrossRefPubMed

43.

Hontela A, Rasmussen JB, Audet C, Chevalier G (1992) Impaired cortisol stress response in fish from environments polluted by PAHs, PCBs, and mercury. Arch Environ Contam Toxicol 22:278–283. https://doi.org/10.1007/BF00212086CrossRefPubMed

44.

Hontela A, Daniel D, Rasmussen JB (1997) Structural and functional impairment of the hypothalamo-pituitary-interrenal axis in fish exposed to bleached kraft mill effluent in the St Maurice River, Quebec. Ecotoxicology 6:1–12. https://doi.org/10.1023/A:1018699405158CrossRef

45.

Norris DO, Donahue S, Dores RM, Lee JK, Maldonado TA, Ruth T, Woodling JD (1999) Impaired adrenocortical response to stress by brown trout, Salmo trutta, living in metal-contaminated waters of the Eagle River, Colorado. Gen Comp Endocrinol 113:1–8. https://doi.org/10.1006/gcen.1998.7177CrossRefPubMed

46.

Girard C, Brodeur JC, Hontela A (1998) Responsiveness of the interrenal tissue of yellow perch (Perca flavescens) from contaminated sites to an ACTH challenge test in vivo. Can J Fis Aquat Sci 55:438–450. https://doi.org/10.1139/f97-224CrossRef

47.

Brodeur JC, Sherwood G, Rasmussen JB, Hontela A (1997) Impaired cortisol secretion in yellow perch (Perca flavescens) from lakes contaminated by heavy metals: in vivo and in vitro assessment. Can J Fish Aquat Sci 54:2752–2758. https://doi.org/10.1139/f97-200CrossRef

48.

Allan SE, Smith BW, Anderson KA (2012) Impact of the deepwater horizon oil spill on bioavailable polycyclic aromatic hydrocarbons in Gulf of Mexico coastal waters. Environ Sci Technol 46:2033–2039. https://doi.org/10.1021/es202942qCrossRefPubMedPubMedCentral

49.

Schwacke LH, Smith CR, Townsend FI et al (2014) Health of common bottlenose dolphins (Tursiops truncatus) in Barataria Bay, Louisiana, following the deepwater horizon oil spill. Environ Sci Technol 48:93–103. https://doi.org/10.1021/es403610fCrossRefPubMed

50.

Venn-Watson S, Colegrove KM, Litz J et al (2015) Adrenal gland and lung lesions in Gulf of Mexico common bottlenose dolphins (tursiops truncatus) found dead following the Deepwater Horizon oil spill. PLoS One 10:e0126538. https://doi.org/10.1371/journal.pone.0126538CrossRefPubMedPubMedCentral

51.

Schwacke LH, Marques TA, Thomas L et al (2022) Modeling population effects of the deepwater Horizon oil spill on a long-lived species. Conserv Biol 36:e13878. https://doi.org/10.1111/cobi.13878CrossRefPubMedPubMedCentral

52.

Smith CR, Rowles TK, Hart LB et al (2017) Slow recovery of Barataria Bay dolphin health following the deepwater horizon oil spill (2013–2014), with evidence of persistent lung disease and impaired stress response. Endang Species Res 33:127–142. https://doi.org/10.3354/esr00778CrossRef

53.

Cartolano MC, Alloy MM, Milton E, Plotnikova A, Mager EM, McDonald MD (2021) exposure and recovery from environmentally relevant levels of waterborne polycyclic aromatic hydrocarbons from deepwater horizon oil: effects on the gulf toadfish stress axis. Environ Toxicol Chem 40:1062–1074. https://doi.org/10.1002/etc.4945CrossRefPubMed

54.

McGruer V, Pasparakis C, Grosell M, Stieglitz JD, Benetti DD, Greer JB, Schlenk D (2019) Deepwater Horizon crude oil exposure alters cholesterol biosynthesis with implications for developmental cardiotoxicity in larval mahi-mahi (Coryphaena hippurus). Comp Biochem Physiol C Toxicol Pharmacol 220:31–35. https://doi.org/10.1016/j.cbpc.2019.03.001CrossRefPubMed

55.

Di Lorenzo M, Barra T, Rosati L, Valiante S, Capaldo A, De Falco M, Laforgia V (2020) Adrenal gland response to endocrine disrupting chemicals in fishes, amphibians and reptiles: a comparative overview. Gen Comp Endocrinol 297:113550. https://doi.org/10.1016/j.ygcen.2020.113550CrossRefPubMed

56.

Gendron AD, Bishop CA, Fortin R, Hontela A (1997) In vivo testing of the functional integrity of the corticosterone-producing axis in mudpuppy (amphibia) exposed to chlorinated hydrocarbons in the wild. Environ Toxicol Chem 16:1694–1706. https://doi.org/10.1002/etc.5620160818CrossRef

57.

Glennemeier KA, Denver RJ (2001) Sublethal effects of chronic exposure to an organochlorine compound on northern leopard frog (Rana pipiens) tadpoles. Environ Toxicol 16:287–297. https://doi.org/10.1002/tox.1035CrossRef

58.

Verreault J, Muir DC, Norstrom RJ et al (2005) Chlorinated hydrocarbon contaminants and metabolites in polar bears (Ursus maritimus) from Alaska, Canada, East Greenland, and Svalbard: 1996–2002. Sci Total Environ 351–352:369–390. https://doi.org/10.1016/j.scitotenv.2004.10.031CrossRefPubMed

59.

Oskam I, Ropstad E, Lie E, Derocher A, Wiig Ø, Dahl E, Larsen S, Skaare JU (2004) Organochlorines affect the steroid hormone cortisol in free-ranging polar bears (Ursus maritimus) at Svalbard, Norway. J Toxicol Environ Health A 67:959–977. https://doi.org/10.1080/15287390490443731CrossRefPubMed

60.

Ropstad E, Oskam IC, Lyche JL, Larsen HJ, Lie E, Haave M, Dahl E, Wiger R, Skaare JU (2006) Endocrine disruption induced by organochlorines (OCs): field studies and experimental models. J Toxicol Environ Health A 69:53–76. https://doi.org/10.1080/15287390500259145CrossRefPubMed

61.

Mohr FC, Lasley B, Bursian S (2008) Chronic oral exposure to bunker C fuel oil causes adrenal insufficiency in ranch mink (Mustela vison). Arch Environ Contam Toxicol 54:337–347. https://doi.org/10.1007/s00244-007-9021-5CrossRefPubMed

62.

Mohr FC, Lasley B, Bursian S (2010) Fuel oil-induced adrenal hypertrophy in ranch mink (Mustela vison): effects of sex, fuel oil weathering, and response to adrenocorticotropic hormone. J Wildl Dis 46:103–110. https://doi.org/10.7589/0090-3558-46.1.103CrossRefPubMed

63.

Sugawara T, Nomura E, Sakuragi N, Fujimoto S (2001) The effect of the aryl hydrocarbon receptor on the human steroidogenic acute regulatory gene promoter activity. J Steroid Biochem Mol Biol 78:253–260. https://doi.org/10.1016/s0960-0760(01)00100-5CrossRefPubMed

64.

Tsuchiya Y, Nakajima M, Itoh S, Iwanari M, Yokoi T (2003) Expression of aryl hydrocarbon receptor repressor in normal human tissues and inducibility by polycyclic aromatic hydrocarbons in human tumor-derived cell lines. Toxicol Sci 72:253–259. https://doi.org/10.1093/toxsci/kfg022CrossRefPubMed

65.

Angelousi A, Nasiri-Ansari N, Karapanagioti A et al (2020) Expression of clock-related genes in benign and malignant adrenal tumors. Endocrine 68:650–659. https://doi.org/10.1007/s12020-020-02246-zCrossRefPubMed

66.

Fommei E, Turci R, Ripoli A, Balzan S, Bianchi F, Morelli L, Coi A (2017) Evidence for persistent organochlorine pollutants in the human adrenal cortex. J Appl Toxicol 37:1091–1097. https://doi.org/10.1002/jat.3460CrossRefPubMed

67.

Hecker M, Hollert H, Cooper R et al (2011) The OECD validation program of the H295R steroidogenesis assay: phase 3. final inter-laboratory validation study. Environ Sci Pollut Res Int 18:503–515. https://doi.org/10.1007/s11356-010-0396-xCrossRefPubMed

68.

Strajhar P, Tonoli D, Jeanneret F, Imhof RM, Malagnino V, Patt M, Kratschmar DV, Boccard J, Rudaz S, Odermatt A (2017) Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids. Toxicology 381:51–63. https://doi.org/10.1016/j.tox.2017.02.010CrossRefPubMed

69.

Ohno S, Shinoda S, Toyoshima S, Nakazawa H, Makino T, Nakajin S (2002) Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells. J Steroid Biochem Mol Biol 80:355–363. https://doi.org/10.1016/s0960-0760(02)00021-3CrossRefPubMed

70.

Nakano Y, Yamashita T, Okuno M, Fukusaki E, Bamba T (2016) In vitro steroid profiling system for the evaluation of endocrine disruptors. J Biosci Bioeng 122:370–377. https://doi.org/10.1016/j.jbiosc.2016.02.008CrossRefPubMed

71.

Zimmer KE, Montaño M, Olsaker I, Dahl E, Berg V, Karlsson C, Murk AJ, Skaare JU, Ropstad E, Verhaegen S (2011) In vitro steroidogenic effects of mixtures of persistent organic pollutants (POPs) extracted from burbot (Lota lota) caught in two Norwegian lakes. Sci Total Environ 409:2040–2048. https://doi.org/10.1016/j.scitotenv.2011.01.055CrossRefPubMed

72.

Li LA, Wang PW (2005) PCB126 induces differential changes in androgen, cortisol, and aldosterone biosynthesis in human adrenocortical H295R cells. Toxicol Sci 85:530–540. https://doi.org/10.1093/toxsci/kfi105CrossRefPubMed

73.

Cheng LC, Li LA (2012) Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis. Toxicol Appl Pharmacol 258:343–350. https://doi.org/10.1016/j.taap.2011.11.017CrossRefPubMed

74.

Lin TC, Chien SC, Hsu PC, Li LA (2006) Mechanistic study of polychlorinated biphenyl 126-induced CYP11B1 and CYP11B2 up-regulation. Endocrinology 147:1536–1544. https://doi.org/10.1210/en.2005-0823CrossRefPubMed

75.

Suwannarin N, Prapamontol T, Isobe T et al (2021) Exposure to organophosphate and neonicotinoid insecticides and its association with steroid hormones among male reproductive-age farmworkers in Northern Thailand. Int J Environ Res Public Health 18:5599. https://doi.org/10.3390/ijerph18115599CrossRefPubMedPubMedCentral

76.

D’Errico MN, Lovreglio P, Drago I, Apostoli P, Soleo L (2016) Influence of occupational and environmental exposure to low concentrations of polychlorobiphenyls and a smoking habit on the urinary excretion of corticosteroid hormones. Int J Environ Res Public Health 13:360. https://doi.org/10.3390/ijerph13040360CrossRefPubMedPubMedCentral

77.

Xu P, Lou X, Ding G, Shen H, Wu L, Chen Z, Han J, Han G, Wang X (2014) Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province. China Sci Total Environ 499:55–61. https://doi.org/10.1016/j.scitotenv.2014.08.057CrossRefPubMed

78.

Silvia SC, Magnarelli G, Rovedatti MG (2020) Evaluation of endocrine disruption and gestational disorders in women residing in areas with intensive pesticide application: an exploratory study. Environ Toxicol Pharmacol 73:103280. https://doi.org/10.1016/j.etap.2019.103280CrossRefPubMed

79.

Giesbrecht GF, Liu J, Ejaredar M, Dewey D, Letourneau N, Campbell T, Martin JW (2016) Urinary bisphenol A is associated with dysregulation of HPA-axis function in pregnant women: findings from the APrON cohort study. Environ Res 151:689–697. https://doi.org/10.1016/j.envres.2016.09.007CrossRefPubMed

80.

Kido T, Dao TV, Ho MD et al (2013) High cortisol and cortisone levels are associated with breast milk dioxin concentrations in Vietnamese women. Eur J Endocrinol 170:131–139. https://doi.org/10.1530/EJE-13-0410CrossRefPubMed

81.

Giesbrecht GF, Ejaredar M, Liu J, Thomas J, Letourneau N, Campbell T, Martin JW, Dewey D (2017) Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study. Environ Health 16:47. https://doi.org/10.1186/s12940-017-0259-8CrossRefPubMedPubMedCentral

82.

Sun X, Li J, Jin S et al (2018) Associations between repeated measures of maternal urinary phthalate metabolites during pregnancy and cord blood glucocorticoids. Environ Int 121:471–479. https://doi.org/10.1016/j.envint.2018.09.037CrossRefPubMed

83.

Pérez-Cadahía B, Lafuente A, Cabaleiro T, Pásaro E, Méndez J, Laffon B (2007) Initial study on the effects of prestige oil on human health. Environ Int 33:176–185. https://doi.org/10.1016/j.envint.2006.09.006CrossRefPubMed

84.

Laffon B, Aguilera F, Ríos-Vázquez J, García-Lestón J, Fuchs D, Valdiglesias V, Pásaro E (2013) Endocrine and immunological parameters in individuals involved in prestige spill cleanup tasks seven years after the exposure. Environ Int 59:103–111. https://doi.org/10.1016/j.envint.2013.05.014CrossRefPubMed

85.

Akinola LK, Uzairu A, Shallangwa GA, Abechi SE (2021) Theoretical study on endocrine disrupting effects of polychlorinated dibenzo-p-dioxins using molecular docking simulation. J Appl Toxicol 41:233–246. https://doi.org/10.1002/jat.4039CrossRefPubMed

86.

Prasanth GK, Divya LM, Sadasivan C (2010) Bisphenol-A can bind to human glucocorticoid receptor as an agonist: an in-silico study. J Appl Toxicol 30:769–774. https://doi.org/10.1002/jat.1570CrossRefPubMed

87.

Sheikh IA, Beg MA (2017) Endocrine disruption: in silico interactions between phthalate plasticizers and corticosteroid binding globulin. J Appl Toxicol 37:1471–1480. https://doi.org/10.1002/jat.3497CrossRefPubMed

88.

Cha J, Hong S, Lee J, Gwak J, Kim M, Kim T, Hur J, Giesy JP, Khim JS (2021) Novel polar AhR-active chemicals detected in sediments of an industrial area using effect-directed analysis based on in vitro bioassays with full-scan high resolution mass spectrometric screening. Sci Total Environ 779:146566. https://doi.org/10.1016/j.scitotenv.2021.146566CrossRefPubMed

89.

Abbott BD (1995) Review of the interaction between TCDD and glucocorticoids in embryonic palate. Toxicology 105:365–373. https://doi.org/10.1016/0300-483x(95)03234-7CrossRefPubMed

90.

Mullen Grey AK, Riddick DS (2011) The aryl hydrocarbon receptor pathway and the response to 3-methylcholanthrene are altered in the liver of adrenalectomized rats. Drug Metab Dispos 39:83–91. https://doi.org/10.1124/dmd.110.035584CrossRefPubMed

91.

Bielefeld KA, Lee C, Riddick DS (2008) Regulation of aryl hydrocarbon receptor expression and function by glucocorticoids in mouse hepatoma cells. Drug Metab Dispos 36:543–551. https://doi.org/10.1124/dmd.107.019703CrossRefPubMed

92.

Pecori Giraldi F, Ambrogio AG (2015) Variability in laboratory parameters used for management of Cushing’s syndrome. Endocrine 50:580–589. https://doi.org/10.1007/s12020-015-0676-9CrossRefPubMedPubMedCentral

93.

Medwid S, Guan H, Yang K (2016) Prenatal exposure to bisphenol A disrupts adrenal steroidogenesis in adult mouse offspring. Environ Toxicol Pharmacol 43:203–208. https://doi.org/10.1016/j.etap.2016.03.014CrossRefPubMed

94.

Oliveira M, Pacheco M, Santos MA (2007) Cytochrome P4501A, genotoxic and stress responses in golden grey mullet (Liza aurata) following short-term exposure to phenanthrene. Chemosphere 66:1284–1291. https://doi.org/10.1016/j.chemosphere.2006.07.024CrossRefPubMed

95.

Knag AC, Taugbøl A (2013) Acute exposure to offshore produced water has an effect on stress- and secondary stress responses in three-spined stickleback Gasterosteus aculeatus. Comp Biochem Physiol C Toxicol Pharmacol 158:173–180. https://doi.org/10.1016/j.cbpc.2013.07.004CrossRefPubMed

96.

Tintos A, Gesto M, Míguez JM, Soengas JL (2008) ß-Naphthoflavone and benzo(a)pyrene treatment affect liver intermediary metabolism and plasma cortisol levels in rainbow trout Oncorhynchus mykiss. Ecotoxicol Environ Saf 69:180–186. https://doi.org/10.1016/j.ecoenv.2007.03.009CrossRefPubMed

97.

Aldegunde M, Soengas J, Ruibal C, Andres MD (1999) Effects of chronic exposure to γ-HCH (Lindane) on brain serotonergic and gabaergic systems, and serum cortisol and thyroxine levels of rainbow trout, Oncorhynchus mykiss. Fish Physiol Biochem 20:325–330. https://doi.org/10.1023/A:1007795121340CrossRef

98.

Pecori Giraldi F, Cavagnini F (2008) Advances in the medical management of Cushing’s syndrome. Exp Opin Pharmacother 9:2423–2433. https://doi.org/10.1517/14656566.9.14.2423CrossRef

99.

Cannavò S, Trimarchi F, Ferraù F (2017) Acromegaly, genetic variants of the aryl hydrocarbon receptor pathway and environmental burden. Mol Cell Endocrinol 457:81–88. https://doi.org/10.1016/j.mce.2016.12.019CrossRefPubMed

Title: Endocrine disruptors, aryl hydrocarbon receptor and cortisol secretion
Authors: F. Pecori Giraldi
F. Ferraù
M. Ragonese
S. Cannavò
Publication date: 18-04-2024
Publisher: Springer International Publishing
Published in: Journal of Endocrinological Investigation
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-024-02371-w

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Endocrine disruptors, aryl hydrocarbon receptor and cortisol secretion

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ACC 2024 Congress Coverage

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Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

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» View more highlights on the ACC 2024 congress hub page