The role of zinc in growth and cell proliferation

The inhibition of growth is a cardinal symptom of zinc deficiency. In anima ls fed a zinc-inadequate diet, both food intake and growth are reduced with in 4-5 d, Despite the concomitant reduction in food intake and growth, redu ced energy intake is not the limiting factor in growth, because force-feedi ng a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, altho ugh well coordinated, mechanisms. Despite the long-term study of zinc metab olism, the first limiting role of zinc in cell proliferation remains undefi ned. Zinc participates in the regulation of cell proliferation in several w ays; it is essential to enzyme systems that influence cell division and pro liferation. Removing zinc from the extracellular milieu results in decrease d activity of deoxythymidine kinase and reduced levels of adenosine(5')tetr aphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis t hrough these systems. Zinc also influences hormonal regulation of cell divi sion. Specifically, the pituitary growth hormone (GH)insulin-like growth fa ctor-I (IGF-I) axis is responsive to zinc status, Both increased and decrea sed circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. Howe ver, growth failure is not reversed by maintaining either GH or IGF-I level s through exogenous administration, which suggests the defect occurs in hor mone signaling, Zinc appears to be essential for IGF-I induction of cell pr oliferation; the site of regulation is postreceptor binding. Overall, the e vidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferat ion in response to IGF-I.