Evidence for thyroxine-growth hormone interaction during brain development.

Abstract

Growth-promoting hormones have complementary and synergistic effects on cell growth. In particular, thyroid hormone–growth hormone (GH) interactions are important in the regulation of somatic development1. Although the requirement of thyroid hormone for normal brain development is well established2, the effects of growth-promoting peptide hormones, including GH, nerve growth factor and insulin, on central nervous system development have not been well characterised. To investigate the possibility of a role for GH in normal CNS development, we have measured its effect on the activity of brain ornithine decarboxylase (ODC), a key enzyme in the synthesis of the polyamines, spermidine and spermine3,4. Previously, we reported increased ODC activity in neonatal rat brain after intraperitoneal (i.p.) or intracranial administration of GH and other growth-promoting peptide hormones5, results which have been supported by other data6,7. We now extend our findings to show that GH stimulation of brain ODC activity depends on the presence of thyroid hormone, even though thyroid hormone, by itself, does not stimulate ODC activity in brain. This is in contrast to liver, where GH and thyroid hormones seem to stimulate ODC activity independently. Our results suggest that thyroid hormone selectively alters or modulates the action of GH in mammalian brain and that abnormal brain development observed in hypothyroidism may in part result from decreased expression of GH activity.