Actions and interactions of thyroid hormone and zinc status in growing rats

Both thyroid hormone (triiodo-L-thyronine, T3) and zinc play important roles in growth and development. The T3 receptor is thought to require zinc to adopt its biologically active conformation. Some of the effects of zinc deficiency, therefore, may be due to loss of zinc from the T3 receptor and impairment of T3 action. This possibility was investigated in growing rats by examining the effects of hypothyroidism and hyperthyroidism in zinc-deficient, pair-fed and control rats. Measurement of serum zinc and T3 confirmed the efficacy of the treatments. Zinc deficiency and hypothyroidism resulted in lower food intake and growth failure, but no interaction was observed between the two treatments. Individual tissue weights were influenced by thyroid status as expected, regardless of zinc status. Both dietary and hormonal treatments influenced serum insulin-like growth factor (IGF)-I in an interactive manner. IGF-I was reduced to a greater extent in zinc-deficient than in pair-fed rats compared with controls. Both hypothyroidism and hyperthyroidism reduced serum IGF-I, and a greater reduction due to hyperthyroidism was apparent in zinc-deficient rats. IGF binding proteins were also influenced by diet and thyroid status. The hepatic expression of mRNA S14 was assessed as a direct index of the nuclear action of T3, but its response was not influenced by dietary treatment. Although confirming the role of both T3 and zinc in the regulation of growth and the somatotrophic axis, the growth failure of zinc deficiency does not appear to be due to impaired T3 function.