Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats

Abstract

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

Thyrocytes, but not C cells, actively undergo growth and folliculogenesis at the periphery of thyroid tissue fragments in three-dimensional collagen gel culture

“…Nor could we confirm the ability of C cell growth at various concentrations of free Ca 2+ in this study. These results together confirm that C cell regeneration is complex, being regulated not only by free Ca 2+ , but also by other physiological factors, such as vitamin D 3 , biogenic amines and polypeptide hormones (Murray 1991;Sawicki 1995;Tiegs et al 1986;Martin-Lacave et al 1998).…”

“…B At 7 and 28 days in culture, C cell number is the highest at 0.78 mM of free Ca 2+ , although there is no statistically significant difference between the paired values at the indicated ranges of free Ca 2+ concentration of free Ca 2+ may bring about C cell hyperplasia, which occurs in some experimental animal models (Zabel 1976). However, our study did not reproduce this result, lending support to the results of other studies that hypercalcemia fails to induce C cell hyperplasia (Tiegs et al 1986;Martin-Lacave et al 1998). The concentration of 0.78 mM free Ca 2+ increased the number of C cells, but there was no statistically significant difference between the various concentrations of free Ca 2+ used in our study.…”

The effect of chronic calcium treatment on thyroid C cells in ovariectomized rats

“…However, Martin-Lacave et al (1998) did not detect such changes affecting C cells in a hypercalcemic state.…”

“…On the contrary, Martin-Lacave et al (1998) concluded that rat C cells do not respond with hypertrophic and hyperplastic changes nor are there significant alterations in serum CT levels in the hypercalcemic state. The recent data of Toda et al (2003) also suggest that various free Ca concentrations reaching porcine thyroid C cells in culture did not change their number significantly, i.e.…”

“…This is in agreement with the in situ hybridization data of Jacobs et al (1983), which showed that high calcium levels do not affect CT mRNA in rat thyroid slices despite the linear increase in CT secretion. Chronic hypercalcemia induced by several different mechanisms is associated with a decrease in thyroid glandular content of CT owing to increased secretion Rix et al, 1984;Martin-Lacave et al, 1998).…”