The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat

Abstract

The effect of vincristine on immunoreactive parathyroid hormone (iPTH) release and parathyroid cell microtubular structures was evaluated in intact, unanaesthetized, and unrestrained rats with indwelling catheters. In overnight fasted rats, blood samples were collected before and at 30, 60 and 120 min after iv vincristine administration in low dosage (0.15 mg/kg) or in higher dosage (0.5 mg/kg) or vehicle (controls) for serum iPTH and calcium determinations. Mean baseline serum iPTH and calcium concentrations were similar in the vincristine-treated and the control rat. Following the low dose vincristine treatment, serum iPTH slightly but significantly declined to 89 \m=+-\5% at 30 min and remained at this low level at 60 and 120 min as compared to those observed in control rat. Similarly, iPTH concentrations after higher doses of vincristine were also significantly decreased to 87 \m=+-\4% at 30 min and to 83 \m=+-\ 4%at 60 min, and 86 \m=+-\7% at 120 min as compared to those observed in the control rat. Serum calcium concentrations were similar in the vincristine\x=req-\ treated and control rats. In the next study, each of the rats received vincristine and vehicle in a random order, 10 days apart. In this study also, mean serum iPTH significantly declined to 85 \m=+-\7% at 60 and 120 min during vincristine treatment as compared with those observed during the vehicle treatment in the same rats. Parathyroid glands were removed from rats between 60 and 120 min after vincristine or vehicle treatments for electron microscopy. Morphometric analysis revealed that the number of microtubules and mean microtubular length of the parathyroid cells were similar in the vincristine-treated rats to those observed in the control rats. Therefore, 1) in the intact rat, even low dosage of vincristine cause significant inhibition of iPTH release and 2) this inhibition occurs in the absence of any morphological alteration in the parathyroid cell microtubular structures.