title: Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats.
abstract: In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.
authors.affiliation: Department of Normal and Pathological Citology and Histology, School of Medicine, University of Seville, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Santos
authors.forename: J C
authors.initials: JC
authors.lastname: Utrilla
authors.forename: E
authors.initials: E
authors.lastname: Conde
authors.forename: A
authors.initials: A
authors.lastname: Hevia
authors.forename: M
authors.initials: M
authors.lastname: Loda
authors.forename: I
authors.initials: I
authors.lastname: Martín-Lacave
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002116:Calcitonin / Q000097:blood / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000378:metabolism* / Q000494:pharmacology; D006934:Hypercalcemia / Q000139:chemically induced*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D002762:Cholecalciferol; D002116:Calcitonin; D002118:Calcium