Highly concentrated calcitriol and its analogues induce apoptosis of parathyroid cells and regression of the hyperplastic gland--study in rats.
BACKGROUND
Controlling hyperplasia of the parathyroid gland (PTG) is important in the management of secondary hyperparathyroidism (SHPT). Regression of the hyperplastic PTG requires a decrease in the number of parathyroid cells (PTCs), so the present study investigated cell death caused by toxic agents or by clinically usable vitamin D metabolites.


METHODS
The PTGs of Sprague-Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet for 12 weeks, were treated with two consecutive direct injections (DI) of calcitriol, maxacalcitol, paricalcitol, doxercalciferol or phosphate-buffered saline containing either 0.01% or 90% ethanol (0.01-ET or 90-ET, respectively). Laboratory data, including serum levels of intact parathyroid hormone (intact-PTH), were obtained before and after the treatments. The PTGs were excised 24 h after the final injection and evaluated for PTC apoptosis using light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) method and DNA electrophoresis.


RESULTS
Treatment with any of the vitamin D metabolites and 90-ET significantly decreased the serum intact-PTH level, but only the latter significantly decreased the serum Ca level. Either treatment markedly increased the number of TUNEL-positive PTCs, but not in PTG treated with 0.01-ET. In PTGs treated with DI of any vitamin D metabolites was there ladder formation on DNA electrophoresis, as well as the characteristic morphological features of apoptosis in both the light and electron microscopic studies.


CONCLUSIONS
DI of vitamin D metabolites may be effective in controlling not only the PTH level, but also PTG hyperplasia, in advanced SHPT by, at least in part, apoptosis-induced cell death. Our study was performed in rats.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D046529:Microscopy, Electron, Transmission; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D010281:Parathyroid Hormone; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium