HORMONES AND THE LUNG .1. THYROID-HORMONES AND GLUCOCORTICOIDS IN LUNG DEVELOPMENT

It has been proposed that thyroid hormones may have a role in the regulation of lung development and the maturation of the surfactant system. The purpose of this study was to examine the effects of exogenous thyroxine (T4) on rat lung development and to investigate possible interactions of this hormone with the glucocorticoids, other hormones implicated in the regulation of lung development. A number of different experimental protocols were utilized: T4 was administered to day 17 and 18 rat fetuses from untreated animals as well as from animals which had been adrenalectomized or treated with the 11‐β‐hydroxylase inhibitor, Metopirone; replacement hydrocortisone was administered to some groups. Sham‐operated and untreated animals were included as controls. Animals were sacrificed from days 19‐22 (term, day 22‐23) of gestation and the fetal lungs were examined. Accelerated lung development was observed in all experimental groups receiving T4. Alveolar epithelial cells were more differentiated in comparison to controls. Glycogen deposits were diminished, cell flattening was more advanced, mitochondria, Golgi complexes and rough endoplasmic reticulum were more prominent, and lamellar bodies, storage sites for pulmonary surfactant, were greatly increased in number. Secretion of lamellar bodies into the alveolar space was also stimulated. The results also indicated that T4 and glucocorticoids act together in the acceleration of lung development. Under conditions of decreased glucocorticoids (Metopirone treatment and adrenalectomy), stimulatory effects of T4 were still evident but less pronounced; hydrocortisone replacement increased the observed stimulation. Maximal acceleration of lung development was observed subsequent to T4 and uncontrolled surgical stress. These results demonstrate that T4 can accelerate rat lung development and that this acceleration is maximal in the presence of glucocorticoids. Copyright © 1979 Wiley‐Liss, Inc.