Thyroidal Influence on Postnatal Lung Development in the Rat*

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Abstract
During the first 2 weeks of postnatal life in the rat, the activities of phosphodiesterase and guanylate cyclase in the lung were found to undergo significant age-related changes. Low constant levels of these enzyme activities during the first 4 postnatal days were followed by a substantial increase to peak levels which plateaued between days 11 and 21 of age, and these changes coincided with the pattern of developmental changes in circulating thyroid hormone levels. When pups were rendered hypothyroid by combined pre- and postnatal treatment with propylthiouracil, the ontogenetic pattern of lung phosphodiesterase was abolished, as were those of serum thyroid hormones; however, that of lung guanylate cyclase was still evident, although slightly depressed. In contrast, treatment of euthyroid pups from the first day of life with daily injections of 1 μg T3 resulted in an advancement of lung phosphodiesterase ontogenesis, whereas that of guanylate cyclase was unaffected. A comparison between euthyroid and hypothyroid lungs between ages 6 and 9 days revealed a significantly lower rate of in vitro [3H]thymidine incorporation into DNA and a significantly higher rate of in vitro [14C]choline incorporation into lipids in the hypothyroid lung. When hypothyroid pups were given a single sc injection of 1 μg T3 between 6 and 9 days of age, serum T3 levels were enormously elevated, and the apparent density of lung T3 receptors was depressed after 6 h; however, these changes were not attended by alterations in lung phosphodiesterase, thymidine incorporation, or choline incorporation. Twenty-four hours after T3 treatment, however, lung phosphodiesterase activity had risen by 34% (P < 0.01), thymidine incorporation into lung DNA had increased by 85% (P < 0.01), and choline incorporation into lung lipids had fallen by 17% (P < 0.05). All of these changes were directed toward euthyroid values and were related to the dose of T3. Whereas the response of lung phosphodiesterase appeared to plateau after the first posttreatment day, that of thymidine incorporation began to diminish by the third day; on the other hand, the rate of choline incorporation was at its nadir 48–72 h after T3 treatment. These results are interpreted to suggest that the thyroidal status of the neonatal rat influences the growth characteristics of the lung, as has been shown for other developing organ systems. It is speculated that T3 may accelerate proliferation and advance the onset of differentiation in the early postnatal rat lung.