Effect of altered thyroid hormone status on rat brain ferritin H and ferritin L mRNA during postnatal development.

ABSTRACT

The iron binding protein ferritin is a heterogeneous mix of 24 heavy (H) and light (L) subunits. The H subunit is associated with iron utilization, while the L subunit is responsible for iron storage. Examination of the developmental pattern of mRNA abundance in rat brain revealed that ferritin L mRNA is highest at birth and declines during the first postnatal week. A similar decline was seen in ferritin H mRNA, but was followed by an increase in ferritin H mRNA in the second postnatal week which continued through postnatal day 21. The pattern of H mRNA regulation is similar to that in previous reports of total ferritin protein in the developing rat brain and is consistent with the fact that brain ferritin is predominately ferritin H. The effect of thyroid hormone on the developmental regulation of ferritin mRNAs was examined by the subcutaneous injection of a single dose of exogenous thyroxine (T(4); 2 microg/g) on postnatal day 1. Hypothyroidism was induced in pregnant dams with propylthiouracil (PTU; 0.05% in drinking water) from gestational day 7. Northern analysis from postnatal days 2-21 showed that T(4) increased ferritin H mRNA throughout development, while ferritin L mRNA was decreased compared to age-matched controls. PTU treatment decreased ferritin H and increased L mRNA in the later stages (days 14-21) of development. Given the distinct functions of ferritin H and L this suggests a role for thyroid hormone in the ability of the brain to regulate stored vs. utilizable iron during critical periods of development.