Vitamin D3 affects expression of thyroid hormone receptor alpha and deiodinase activity in liver of MNU-treated Sprague-Dawley rats.
1alpha,25-dihydroxyvitamin D3 and its analogue, Seocalcitol (EB1089), are able to reverse or slow the process of carcinogenesis in experimental models and cell cultures. The aim of this study was to investigate the effect of administration vitamin D or Seocalcitol to female Sprague-Dawley rats with 1-methyl-1-nitrosourea (MNU)-induced carcinogenesis of mammary glands on binding characteristics and mRNA levels of thyroid hormone receptors (TRs). Chemopreventive administration of vitamin D caused significant reduction of animal body weight. The expression of TRalpha mRNA was significantly higher in liver of animals treated with vitamin D after detection of first tumour. In our experiment, administration of vitamin D or Seocalcitol significantly reduced KA (group MNU+Seo; MNU+D) and increased Bmax (group MNU+Seo) of thyroid receptors in liver when compared to healthy animals. We show that the activity type I 5'-deiodinase was significantly decreased in livers of animals treated with vitamin D. The data from our in vivo experiment has clearly shown, for the first time, that vitamin D but not Seocalcitol i) may affect the body weight of animals, ii) can cause an increase in the expression of TRalpha in rat liver, remaining the functionality of the TRs unaffected, and iii) is responsible for type I iodothyronine 5'-deiodinase activity decrease in rat liver, remaining the expression of the enzyme unaffected.
Macejová
Dana
D
Office of the Slovak Academy of Sciences, Slovak Academy of Sciences, Vlárska 3, 833 06 Bratislava, Slovakia. ueenmace@savba.sk
Ondková
Slavomíra
S
Brtko
Július
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D002762:Cholecalciferol; D008770:Methylnitrosourea; D004247:DNA; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D002117:Calcitriol; C078903:seocalcitol