Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats

• Fernández-Santos, J.M. ^[1] ; Utrilla, J.C. ^[1] ; Conde, E. ^[1] ; Hevia, A. ^[1] ; Loda, M. ^[2] ; Martín Lacave, Inés ^[1]
  1. [1] Universidad de Sevilla

     Universidad de Sevilla

     Sevilla, España

     
  2. [2] Dana–Farber Cancer Institute

     Dana–Farber Cancer Institute

     City of Boston, Estados Unidos

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 2, 2001, págs. 407-414
• Idioma: inglés
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• Resumen

  • 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 Ccells. 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-ce!ls, 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-ce!l 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 (CaCI2). Under these long-term vitaminD3-hypercalcemic conditions, calcium, active metabolites of vitamin 0 3, 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 0 3 results in a decrease in hormone biosynthetic activities of both PTH and CTproducing 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.