Direct injection of calcitriol or its analog improves abnormal gene expression in the hyperplastic parathyroid gland in uremia.

Abstract

AIMS: In this study, we investigated the effects of direct injection (DI) of calcitriol or maxacalcitol into the hyperplastic parathyroid gland (PTG) on altered gene expression related to the advanced status of secondary hyperparathyroidism (SHPT). METHODS: Sprague-Dawley rats were 5/6-nephrectomized (uremic) or sham-operated (normal). In each uremic rat, one of the bilateral PTG was treated by DI of calcitriol (PTG(CAL)) or maxacalcitol (PTG(OCT)), and the other gland was treated with control solution (PTG(CONT)). The PTG were evaluated for levels of expression of various mRNA and immunohistochemical staining of proliferating cell nuclear antigen (PCNA). RESULTS: Significant differences in levels of expression of mRNA and PCNA were confirmed between the uremic and normal groups. In PTG(CAL) and PTG(OCT), expressions of almost all mRNA and PCNA were significantly improved; both agents were able to normalize the abnormalities of the uremic PTG, in contrast to the baseline and individual PTG(CONT). However, the difference in effect between PTG(CAL) and PTG(OCT) was only small. CONCLUSION: Our results suggest that very high concentrations of calcitriol or maxacalcitol in the PTG improve abnormal gene expression and proliferation activity of parathyroid cells, and might explain the better control of SHPT using the DI technique.