VITAMIN-D-3, LACTOSE, AND XYLITOL STIMULATE CHROMAFFIN CELL-PROLIFERATION IN THE RAT ADRENAL-MEDULLA

Chronic consumption by rats of diets rich in sugars or sugar alcohols leads to an increased incidence of pheochromocytomas. This relationshi p is hypothesized to be based on altered Ca2+ homeostasis due to incre ased intestinal Ca2+ absorption. Other agents associated with pheochro mocytomas in rats in long-term toxicity studies have been shown to inc rease chromaffin cell proliferation, leading to the suggestion that th e tumors occur secondarily to increased chromaffin cell turnover. We h ave demonstrated marked stimulation of chromaffin cell proliferation b y vitamin D-3, a potent stimulus to Ca2+ absorption not previously ass ociated with adrenal medullary toxicity. This effect is detectable dur ing the first week of dietary supplementation and persists throughout a 4-week time course. Lactose and xylitol, representative of sugars an d sugar alcohols associated with pheochromocytomas, are also mitogenic but to a lesser extent, with their effects first detectable during We ek 4 of dietary supplementation. Vitamin D-3, its active metabolite ca lcitriol, lactose, and xylitol all fail to stimulate proliferation of rat chromaffin cells in vitro. The mitogenic effects of these agents m ay be mediated presynaptically in vivo. The data suggest that altered Ca2+ homeostasis may increase chromaffin cell proliferation and suppor t the hypothesis that diets containing high concentrations of sugars a nd sugar alcohols cause pheochromocytomas in rats secondarily by this mechanism. (C) 1996 Academic Press, Inc.