Differential effects of cadmium on the gene expression of seven-transmembrane-spanning receptors and GAPDH in the rat testis.

Cadmium (Cd) is a widely spread toxicant with endocrine disrupting properties. Under experimental conditions it suppresses sex steroid synthesis in the male as well as the female. Testicular steroidogenesis is primarily regulated by gonadotropins, but is also influenced by catecholamines. We have previously shown that Cd exposure affects rat testosterone synthesis by down-regulating luteinizing hormone (LH) receptor mRNA expression. In this study, rats were given 10 micromol/kg Cd subcutaneously and sacrificed 0.48-144 h later. We investigated the effects of Cd on testicular gene expression of two adrenergic receptors. In addition, mRNA levels of the androgen-regulated house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured. In contrast to the suppressive influence on LH receptor expression Cd lacked effect on the expression of alpha(1A)- and beta(2)-adrenergic receptors. GAPDH gene expression, on the other hand, was up-regulated 1.6-fold after exposure to 10 micromol/kg Cd. These data suggest that the influence of Cd on testicular gene expression involves a specific effect on the LH receptor and not a general effect on seven-transmembrane-spanning receptors. Also, data indicate that the increased expression of GAPDH may be secondary to Cd-induced testosterone deprivation, suggesting future studies of androgen-regulated genes in the toxicity of Cd.