Cadmium-induced changes in Per 1 and Per 2 gene expression in rat hypothalamus and anterior pituitary: Effect of melatonin

Chronic cadmium (Cd) administration affects the circadian release of pituitary hormones in rats. To assess whether Cd modifies expression of two major clock genes, period (Per) 1 and Per 2, in the hypothalamic–pituitary unit and to what extent the changes could be prevented by melatonin, rats were exposed to CdCl2 (5 ppm in drinking water) with or without melatonin (3 μg/mL drinking water) for 1 month and were killed at two time intervals, i.e. a the beginning of the rest span (09:00 h) and at the middle of the activity span (01:00 h). Hypothalamic and pituitary mRNA levels encoding Per 1 and Per 2 were measured by real-time PCR analysis. Cd treatment decreased expression of hypothalamic Per 1 gene at both time intervals, of hypothalamic Per 2 gene at 01:00 h, and of adenohypophysial Per 1 and Per 2 genes at 09:00 h. Melatonin administration counteracted most of the effects of Cd and augmented hypothalamic Per 2, and adenohypophysial Per 1 and Per 2 gene expression. The results indicate that Cd administered chronically in the drinking water to rats affected expression of clock genes in the hypothalamic–pituitary unit, an effect prevented by melatonin.