Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone.
Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, we studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 micrograms/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T4, T4, T3, cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolactin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitaries. After incubation of pituitary cells with 0.1-10 microM Pb2+ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release. Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, 45Ca2+ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 microM lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007223:Infant; D007700:Kinetics; D007855:Lead Poisoning / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D002118:Calcium