Short stature, one of the classic stigmata of childhood lead (pb) poisoning, has received almost no contemporary consideration. Analysis of the National Health and Nutrition Examination Survey (NHANES II) of 1976-1980 data on 2695 children ages 6 months - 7 years showed a significant, independent, negative correlation of blood lead (PbB) with height, weight and chest circumference. The typical explanation which associates nutritional deficiency and high lead exposure in children at socioeconomic risk, was not statistically verified. There are several plausible biologic mechanisms for growth retardation by lead, with strong evidence for neuroendocrine toxicity. This prompted preliminary in vitro studies of possible mechanisms of toxicity. Rat pituitary cells incubated in the presence of 0.1-100 MuM Pb++ showed a dose related inhibition of TRH-induced TSH release. Additional kinetic analysis of calcium distribution in anterior pituitary slices after incubation with Pb++ implicates a Pb/Ca interaction.
The specific aims of the proposed study are: 1) Test, in pituitary cells of immature and mature rats, the effect of lead on the response to TRH, GnRH and GHRF as measured by hormone release and morphology. 2) Examine the mechanisms by which Pb might inhibit TRH induced TSH release by studying, in thyrotrophs of immature rats, the effect of Pb on. a) 3H-TRH binding to membrane receptors, b) voltage and receptor-mediated calcium channels, c) intracellular distribution of calcium, and d) the activation of intracellular calcium receptors such as calmodulin and protein kinase C.
| Camoratto, A M; White, L M; Lau, Y S et al. (1993) Effect of exposure to low level lead on growth and growth hormone release in rats. Toxicology 83:101-14 |
| Lau, Y S; Camoratto, A M; White, L M et al. (1991) Effect of lead on TRH and GRF binding in rat anterior pituitary membranes. Toxicology 68:169-79 |
