Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.
High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah University Hospital, Jerusalem, Israel.
T
T
Naveh-Many
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F
Raue
A
A
Grauer
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Silver
D000199:Actins / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000097:blood / Q000235:genetics*; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage; D002279:Carcinoma 256, Walker / Q000150:complications; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006934:Hypercalcemia / Q000235:genetics*; D006996:Hypocalcemia / Q000235:genetics*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology; D014158:Transcription, Genetic
D000199:Actins; D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D013004:Somatostatin; D002116:Calcitonin; D002117:Calcitriol; D002118:Calcium