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Tributyltin chloride and triphenyltin chloride inhibit steroid hormone secretion by mouse Leydig cells TM3 and human adrenocortical cells H295R Cover

Tributyltin chloride and triphenyltin chloride inhibit steroid hormone secretion by mouse Leydig cells TM3 and human adrenocortical cells H295R

Open Access
|Jul 2026

References

  1. Agency for Toxic Substances and Disease Registry (ATSDR). 2005. Toxicological profile for tin. Atlanta, GA: U.S. Department of Health and Human Services. http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=543&tid=98.
  2. Antizar-Ladislao B. Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment: A review. Environ Int 34, 292–308, 2008.
  3. de Araujo JFP, Podratz PL, Merlo E, Sarmento IV, da Costa CS, Nino OMS, Faria RA, Freitas Lima LC, Graceli JB. Organotin exposure and vertebrate reproduction: A review. Front Endocrinol (Lausanne) 9, 64, 2018.
  4. Boulogne B, Levacher C, Durand P, Habert R. Retinoic acid receptors and retinoid X receptors in the rat testis during fetal and postnatal development: immunolocalization and implication in the control of the number of gonocytes. Biol Reprod 61, 1548–1557, 1999.
  5. Boyer IJ. Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals. Toxicology 55, 253–298, 1989.
  6. Brtko J, Dvorak Z. Triorganotin compounds--ligands for “rexinoid” inducible transcription factors: biological effects. Toxicol Lett 234, 50–58, 2015.
  7. Brtko J, Dvorak Z. Natural and synthetic retinoid X receptor ligands and their role in selected nuclear receptor action. Biochimie 179, 157–168, 2020.
  8. Chen H, Ge RS, Zirkin BR. Leydig cells: from stem cells to aging. Mol Cell Endocrinol 306, 9–16, 2009.
  9. Chen P, Song Y, Tang L, Zhong W, Zhang J, Cao M, Chen J, Cheng G, Li H, Fan T, Kwok HF, Wang J, Yang C, Xiao W. Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells. J Hazard Mater 448, 130785, 2023.
  10. Delgado Filho VS, Lopes PF, Podratz PL, Graceli JB. Triorganotin as a compound with potential reproductive toxicity in mammals. Braz J Med Biol Res 44, 958–965, 2011.
  11. Dufour JM, Kim KH. Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors. Biol Reprod 61, 1300–1308, 1999.
  12. European Union (EU). 2006. Revised assessment of the risks to health and the environment associated with the use of the four organotin compounds TBT, DBT, DOT and TPT.
  13. Gaemers IC, van Pelt AM, van der Saag PT, Hoogerbrugge JW, Themmen AP, de Rooij DG. Effect of retinoid status on the messenger ribonucleic acid expression of nuclear retinoid receptors alpha, beta, and gamma, and retinoid X receptors alpha, beta, and gamma in the mouse testis. Endocrinology 138, 1544–1551, 1997.
  14. Gaemers IC, van Pelt AM, van der Saag PT, Hoogerbrugge JW, Themmen AP, de Rooij DG. Differential expression pattern of retinoid X receptors in adult murine testicular cells implies varying roles for these receptors in spermatogenesis. Biol Reprod 58, 1351–1356, 1998.
  15. Graceli JB, Sena GC, Lopes PF, Zamprogno GC, da Costa MB, Godoi AF, Dos Santos DM, de Marchi MR, Dos Santos Fernandez MA. Organotins: a review of their reproductive toxicity, biochemistry, and environmental fate. Reprod Toxicol 36, 40–52, 2013.
  16. Hecker M, Newsted JL, Murphy M B, Higley EB, Jones PD, Wu R, Giesy JP. Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: hormone production. Toxicol Appl Pharmacol 217, 114−124, 2006.
  17. Hecker M, Hollert H, Cooper R, Vinggaard AM, Akahori Y, Murphy M, Nellemann C, Higley E, Newsted J, Laskey J, Buckalew A, Grund S, Maletz S, Giesy J, Timm G. The OECD validation program of the H295R steroido-genesis assay: Phase 3. Final inter-laboratory validation study. Environ Sci Pollut Res Int 18, 503–515, 2011.
  18. Hollert H, Giesy J. The OECD validation program of the H295R Steroidogenesis Assay for the identification of in vitro inhibitors and inducers of testosterone and estradiol production. Phase 2: Inter-laboratory pre-validation studies (8 pp). Environ Sci Pollut Res Int 14, 23–30, 2007.
  19. Hu J, Zhang D, Yan Z, Cheng Y. The in vitro effects of trimethyltin on the androgen biosynthesis of rat immature Leydig cells. Toxicology 444, 152577, 2020.
  20. Kastner P, Mark M, Mark L, Dierich A, Chambon P. Abnormal spermatogenesis in RXR mutant mice. Genes Dev 10, 80–92, 1996.
  21. Li G, Chang X, Zhao Y, Li D, Kang X. Dibutyltin (DBT) inhibits in vitro androgen biosynthesis of rat immature Leydig cells. Toxicology 456, 152779, 2021.
  22. Li X, Tian E, Wang Y, Wen Z, Lei Z, Zhong Y, Ge RS. Stem Leydig cells: Current research and future prospects of regenerative medicine of male reproductive health. Semin Cell Dev Biol 121, 63–70, 2022.
  23. Lo S, Allera A, Albers P, Heimbrecht J, Jantzen E, Klingmuller D, Steckelbroeck S. Dithioerythritol (DTE) prevents inhibitory effects of triphenyltin (TPT) on the key enzymes of the human sex steroid hormone metabolism. J Steroid Biochem Molec Biol 84, 569–576, 2003.
  24. Lima D, Reis-Henriques M, Silva R, Santos A, Castro LFC, Santos M. Tributyltin-induced imposex in marine gastro-pods involves tissue-specific modulation of the retinoid X receptor. Aquat Toxicol 101, 221–227, 2011.
  25. Maglich JM, Kuhn M, Chapin RE, Pletcher MT. More than just hormones: H295R cells as predictors of reproductive toxicity. Reprod Toxicol 45, 77−86, 2014.
  26. Mitra S, Srivastava A, Khanna S, Khandelwal S. Consequences of tributyltin chloride induced stress in Leydig cells: an ex-vivo approach. Environ Toxicol Pharmacol 37, 850–60, 2014.
  27. Nagata T, Kanno Y, Ozato K, Taketo M. The mouse Rxrb gene encoding RXR beta: genomic organization and two mRNA isoforms generated by alternative splicing of transcripts initiated from CpG island promoters. Gene 142, 183–189, 1994.
  28. Nakajima Y, Sato G, Ohno S, Nakajin S. Organotin compounds suppress testosterone production in Leydig cells from neonatal pig testes. J Health Sci 49, 514–519, 2003.
  29. Nakajima Y, Sato G, Ohno S, Nakajin S. Tributyltin chloride suppresses the P450cl7 transcription involved in testosterone production induced by gonadotropin stimulation in cultured pig Leydig cells. Environ Toxicol Pharmacol 20, 11–17, 2005.
  30. Nakanishi T. Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor. J Toxicol Sci 33, 269–276, 2008.
  31. OECD. Test Guideline No. 456 H295R Steroidogenesis Assay; OECD Guidelines for the Testing of Chemicals, Section 4; OECD, 2022.
  32. Ohno S, Nakajima Y, Nakajin S. Triphenyltin and tributyltin inhibit pig testicular 17beta-hydroxysteroid dehydrogenase activity and suppress testicular testosterone biosynthesis. Steroids 70, 645–651, 2005.
  33. Okoro HK, Fatoki OS, Adekola FA, Ximba BJ, Snyman RG, Opeolu B. Human exposure, biomarkers, and fate of organotins in the environment. Rev Environ Contam Toxicol 213, 27–54, 2011.
  34. Peivasteh-Roudsari L, Barzegar-Bafrouei R, Sharifi KA, Azimisalim S, Karami M, Abedinzadeh S, Asadinezhad S, Tajdar-Oranj B, Mahdavi V, Alizadeh AM, Sadighara P, Ferrante M, Conti GO, Aliyeva A, Mousavi Khaneghah A. Origin, dietary exposure, and toxicity of endocrine-disrupting food chemical contaminants: a comprehensive review. Heliyon 9, e18140, 2023.
  35. Rehurkova E, Bajard L, Sovadinova I. In vitro models for testicular steroidogenesis: current status and future perspectives. Arch Toxicol 2026 Apr 28.
  36. Risk & Policy Analysts Limited (RPA). 2005. Risk assessment studies on targeted consumer applications of certain organotins compounds. Norfolk, United Kingdom: The European Comission.
  37. Saez JM. Leydig cells: endocrine, paracrine, and autocrine regulation. Endocr Rev 15, 574–626, 1994.
  38. Sanderson JT, Boerma J, Lansbergen GW, van den Berg M. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol Appl Pharmacol 182, 44–54, 2002.
  39. Scott HM, Mason JI, Sharpe RM. Steroidogenesis in the fetal testis and its susceptibility to disruption by exogenous compounds. Endocr Rev 30, 883e925, 2009.
  40. Stefanizzi V, Minutolo A, Valletta E, Carlini M, Cordero FM, Ranzenigo A, Prete SP, Cicero DO, Pitti E, Petrella G, Matteucci C, Marino-Merlo F, Mastino A, Macchi B. Biological evaluation of triorganotin derivatives as potential anticancer agents. Molecules 28, 3856, 2023.
  41. Sousa ACA, Pastorinho MR, Takahashi S, Tanabe S. History on organotin compounds, from snails to humans. Environ Chem Lett 12, 117–137, 2014.
  42. Wang BA, Li M, Mu YM, Lu ZH, Li JY. [Effects of tributyltin chloride (TBT) and triphenyltin chloride (TPT) on rat testicular Leydig cells]. Zhonghua Nan Ke Xue 12, 516–519, 2006.
  43. Wang GS, Liang A, Dai YB, Wu XL, Sun F. Expression and localization of retinoid receptors in the testis of normal and infertile men. Mol Reprod Dev 87, 978–985, 2020.
  44. Whalen MM, Loganathan BG, Kannan K. Immunotoxicity of environmentally relevant concentrations of butyltins on human natural killer cells in vitro. Environ Res 81, 108–116, 1999.
  45. World Health Organization (WHO). 2006. Mono- and disubstituted methyltin, butyltin, and octyltin compounds.
  46. Yan X, He B, Liu L, Qu G, Shi J, Liao C, Hu L, Jiang G. Organotin exposure stimulates steroidogenesis in H295R Cell via cAMP pathway. Ecotoxicol Environ Saf 156, 148–153. 2018a.
  47. Yan X, He B, Hu L, Gao J, Chen S, Jiang G. Insight into the endocrine disrupting effect and cell response to butyl-tin compounds in H295R cell: Evaluated with proteomics and bioinformatics analysis. Sci Total Environ 628–629, 1489–1496, 2018b.
  48. Yang F, Li X, Wang M, Lan X, Zhang J, Li J, Chang D, Yu X. The role of environmental endocrine disruptors on Leydig cell death and senescen. World J Mens Health 43, 477–491, 2025.
  49. Yi AX, Leung KM, Lam MH, Lee JS, Giesy JP. Review of measured concentrations of triphenyltin compounds in marine ecosystems and meta-analysis of their risks to humans and the environment. Chemosphere 89, 1015–1025, 2012.
DOI: https://doi.org/10.2478/enr-2026-0016 | Journal eISSN: 1336-0329 | Journal ISSN: 1210-0668
Language: English
Page range: 159 - 171
Published on: Jul 5, 2026
In partnership with: Paradigm Publishing Services

© 2026 Dana Macejova, Alzbeta Berenikova, Julius Brtko, Lucia Toporova, Alzbeta Bujnakova Mlynarcikova, Sona Scsukova, published by Slovak Academy of Sciences, Institute of Experimental Endocrinology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.