Thyroid hormones play an important role in mammalian fetal lung development. Delayed fetal lung ultrastructural maturation is observed in the Hyt/Hyt mouse which has primary hypothyroidism due to a point mutation(Pro-556-Leu) in the β subunit of the TSH receptor (Ped. Res.380-386,1994). Thyroid transcriptional factor 1 (T.T.F.-1) and surfactant protein C (SP-C) play an important role in fetal lung function and type II cell differentiation. The effect of primary hypothyroidism on the developmental expression of lung SP-C or TTF-1 has not been studied. Hypothyroid (Hyt/Hyt) mice, characterized by high serum TSH and low serum free T4 concentration, were made euthyroid by T3 supplementation. These mice were mated to produce hypothyroid (Hyt/hyt) pups. Balb-c mice served as euthyroid controls. Mice were killed on d 18 of pregnancy (term≈19d, vaginal plug=d 1). Immunostaining of fetal lung for SP-C was done using polyclonal antibody. The intensity of the immunoreactivity for SP-C was scored on a scale of 0 to 3 in 0.5 increments. Fetal lung gene expression for T.T.F.-1 and SP-C was determined by Northern analysis and densitometry. All data Mean ±SEM, * P<0.02 There was a linear relationship between the gene expression for T.T.F.-1 and SP-C in these mice (r=0.86). We conclude that primary hypothyroidism causes a delay in the gene expression for TTF-1 and SP-C in the fetal lung. Table

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