Mechanisms by which lead depresses linear and ponderal growth in weanling rats.

Lead is known to reduce linear and ponderal growth in children, even at levels of exposure common in the general population. The mechanism involved is not known. The present study was conducted in order to establish the role of food consumption and insulin-like growth factor (IGFI), also commonly known as somatomedin C (SmC), in lead-induced reduction in growth in weanling rats. A further purpose was to test the hypothesis that depressed growth could be prevented by administration of growth hormone and thyroxine, a procedure which prevents arrested growth due to hypophysectomy. Treatment with growth hormone in combination with thyroxine had no effect on depressed growth or food consumption. The reduction in linear and ponderal growth due to lead (approximately 17%) could be largely though not completely accounted for on the basis of reduced food consumption, apparently by a mechanism not involving growth hormone or thyroxine (see above). Plasma SmC was reduced in proportion to reduced food intake, regardless of whether due to Pb or to restriction of food intake in a pair-feeding experiment thereby ruling out an effect of lead on SmC synthesis or activity other than through reduced food consumption. The experiments leading to these conclusions all involved administration of lead in the drinking water, suggesting the possibility that reduced food consumption was peripherally mediated as a result of contact of lead with appetite-depressant receptors in the gastrointestinal tract, e.g., taste receptors. An additional experiment therefore was conducted comparing food consumption and growth resulting from oral lead administration to subcutaneous administration. Similar depressant effects on food consumption and growth resulted at similar concentrations of lead and zinc protoporphyrin in blood. These effects were significantly greater following oral administration, however, suggesting that lead depresses appetite by both a systemic mechanism and one operating at the level of the gastrointestinal tract.