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 CdCl(2) (5ppm in drinking water) with or without melatonin (3 microg/mL drinking water) for 1 month and were killed at two time intervals, i.e. a the beginning of the rest span (09:00h) and at the middle of the activity span (01:00h). 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 01:00h, and of adenohypophysial Per 1 and Per 2 genes at 09:00h. 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.
Cano
Pilar
P
Department of Biochemistry and Molecular Biology III, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
Poliandri
Ariel H B
AH
Jiménez
Vanessa
V
Cardinali
Daniel P
DP
Esquifino
Ana I
AI
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539024:Per1 protein, rat; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D002104:Cadmium; D008550:Melatonin