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

Authors

Dana Macejova, Alzbeta Berenikova, Julius Brtko, Lucia Toporova, Alzbeta Bujnakova Mlynarcikova, Sona Scsukova

Published in

Endocrine regulations. Volume 60. Issue 1. Pages 159-171. Jan 01, 2026. Epub Jul 05, 2026.

Abstract

Objective. To find a possible balance between toxicity and potential anticancer activity of novel triorganotin compounds, retinoid X receptor (RXR) agonists, investigation the relationship between the structure, physicochemical properties, and biological activity of these compounds in non-tumorigenic and tumorigenic cells is required. This study aimed to investigate the effects of selected triorganotin compounds, tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPTCl), on viability and steroidogenic function of non-tumorigenic mouse Leydig cell line TM3 and human adrenocortical carcinoma cell line H295R. Methods. Gene and protein expression of RXR subtypes (RXRα, RXRβ, RXRγ) in TM3 Leydig cells was identified by qualitative PCR and immunofluorescence. The potency of TBT-Cl and TPTCl to induce mRNA expression of RXR subtypes in TM3 cells was analyzed by semi-quantitative real-time PCR. After exposure of TM3 and H295R cells to different concentration of TBT-Cl and TPT-Cl (0.1 nM-1 µM) for different time periods (24, 48, 72 h), cell viability was evaluated by detection of mitochondrial activity (MTT assay) and membrane integrity (LDH assay), and steroid hormone (testosterone, cortisol) levels in culture media were measured by radioimmunoassay. Results. Qualitative PCR and immunofluorescence examination revealed that all RXR subtypes, RXRα, RXRβ, RXRγ, are expressed in TM3 Leydig cells. TBT-Cl (500 nM) activated the expression of RXRα and RXRβ and at a concentration of 100 nM, RXRγ expression. TPT-Cl (10 and 100 nM) activated the expression of all three RXR subtypes and at a concentration of 500 nM, reduced RXRα expression similar to 9cRA (100 nM). Both compounds, TBT-Cl and TPT-Cl, induced a dose- and time-dependent significant decrease in the viability of TM3 Leydig cells and, in addition, TBT-Cl (500 nM and 1 µM) significantly inhibited androstenedione-induced testosterone secretion by these cells. Similarly, both tested triorganotin compounds (1 µM) significantly decreased viability of adrenocortical H295R cells and basal as well as forskolin-stimulated testosterone and cortisol secretions by these cells. Conclusion. TBT-Cl and TPT-Cl compromised cell viability and induced important functional alteration in Leydig cells probably through RXR activation with potential implications for male reproductive function. Endocrine-disrupting properties of TBT-Cl and TPT-Cl were demonstrated in adrenocortical H295R cells.

PMID:
42406097
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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