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Enan, E. et al.

Enan, El-Sabeawy, Overstreet, Matsumura, Lasley,

Mechanisms of gender-specific TCDD-induced toxicity in guinea pig adipose tissue.

After treatment with TCDD, the activities of cytosolic AhR- associated c-Src kinase, microsomal protein kinase C (nPKC epsilon), microsomal c-Src kinase, nuclear p44/42 MAPK, c-Jun N terminus kinase, and the amount of microsomal pan-Ras protein were different in males and females. TCDD did not decrease body or adipose tissue weights in transgenic src-deficient male mice as compared to their wild-type littermates, and the activity of AhR- associated c-Src kinase was not increased by TCDD in src-deficient male mice. Similar results were obtained when TCDD was given to male guinea pigs treated with the Src-kinase inhibitor, geldanamycin. Treatment with estradiol protected male guinea pigs from TCDD-induced wasting. TCDD induced similar changes in protein tyrosine kinase activity in adipose tissues of castrated male and intact female guinea pigs. The gender-specific mechanisms of TCDD-induced toxicity appear to involve c-Src kinase, nPKC epsilon, and pan-Ras, as well as overlap in the cytosolic signal transduction pathways of TCDD and sex steroids.[1]

References

Mechanisms of gender-specific TCDD-induced toxicity in guinea pig adipose tissue. Enan, E., El-Sabeawy, F., Overstreet, J., Matsumura, F., Lasley, B. Reprod. Toxicol. (1998) [Pubmed]

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