Pig Leydig cell culture: a useful in vitro test for evaluating the testicular toxicity of compounds
- PMID: 1850172
- DOI: 10.1016/0041-008x(91)90120-4
Pig Leydig cell culture: a useful in vitro test for evaluating the testicular toxicity of compounds
Abstract
In vivo studies have shown that the testis is a target organ for drugs and chemicals. In order to evaluate the testicular toxicity of compounds and to identify the mechanisms of their toxicity, we have developed a miniaturized primary culture of immature pig Leydig cells. Five well-known drugs with differing mechanisms of toxicity on testicular functions were tested to validate the model. Testosterone and progesterone secretion were measured to evaluate testicular function. Cell viability was assessed quantitatively using a colorimetric assay based on the reduction of a tetrazolium salt (3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide) which stains viable cells only, thus allowing discrimination between specific inhibitors of Leydig cell function and nonspecific cytotoxic drugs. Ketoconazole and aminoglutethimide inhibited both testosterone and progesterone secretion, but without modifying cell viability. Spironolactone specifically blocked testosterone secretion and increased progesterone concentration without inducing cell mortality. Cycloheximide altered testicular steroid secretion by another mechanism of action. Chlorpromazine, which interferes with the secretion of gonadotropins in vivo, produced a significant inhibition of progesterone and testosterone secretion as a result of the cytotoxic effects of the drug. In conclusion, this in vitro test enables one to discriminate accurately between specific and nonspecific inhibitors of steroidogenesis and could reduce the number of false positives when screening for potential testicular toxins.
Similar articles
-
Ex vivo and in vitro testis and ovary explants: utility for identifying steroid biosynthesis inhibitors and comparison to a Tier I screening battery.Toxicol Sci. 1998 Nov;46(1):61-74. doi: 10.1006/toxs.1998.2560. Toxicol Sci. 1998. PMID: 9928669
-
Testicular and germ cell toxicity: in vitro approaches.Reprod Toxicol. 1993;7 Suppl 1:17-22. doi: 10.1016/0890-6238(93)90065-f. Reprod Toxicol. 1993. PMID: 8400636 Review.
-
Functional activity of rat testicular cells in culture.Biochem Int. 1988 Feb;16(2):311-21. Biochem Int. 1988. PMID: 3163249
-
The interaction of Sertoli and Leydig cells in the testicular toxicity of tri-o-cresyl phosphate.Toxicol Appl Pharmacol. 1990 Jul;104(3):483-95. doi: 10.1016/0041-008x(90)90170-y. Toxicol Appl Pharmacol. 1990. PMID: 2385838
-
Dependence of gonadotropin-induced steroidogenesis upon RNA and protein synthesis in the interstitial cells of the rat testis.Biochim Biophys Acta. 1975 Dec 5;411(2):222-30. doi: 10.1016/0304-4165(75)90302-5. Biochim Biophys Acta. 1975. PMID: 172138
Cited by
-
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).Sci Rep. 2018 Feb 1;8(1):2118. doi: 10.1038/s41598-018-20266-8. Sci Rep. 2018. PMID: 29391432 Free PMC article.
-
Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-induced male rats.Iran J Reprod Med. 2014 Mar;12(3):209-16. Iran J Reprod Med. 2014. PMID: 24799882 Free PMC article.
-
In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat.Biol Reprod. 2011 Jul;85(1):51-61. doi: 10.1095/biolreprod.110.089920. Epub 2011 Mar 9. Biol Reprod. 2011. PMID: 21389346 Free PMC article.
-
In utero exposure to di-(2-ethylhexyl) phthalate decreases mineralocorticoid receptor expression in the adult testis.Endocrinology. 2009 Dec;150(12):5575-85. doi: 10.1210/en.2009-0847. Epub 2009 Oct 9. Endocrinology. 2009. PMID: 19819939 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources