Effect of prenatal glucocorticoid on fetal lung ultrastructural maturationin hyt/hyt mice with primary hypothyroidism

Glucocorticoids (GC) and thyroid hormones (TH) accelerate fetal lung matura tion. Though GC are used clinically, the mechanisms of GC-induced fetal lun g maturity remain unclear. Prenatal GC increase fetal TH activity in humans and in animals. Thus, it is possible that increased fetal TH activity afte r prenatal GC plays a role in accelerating fetal lung maturation. However, this hypothesis has remained untested due to the lack of a suitable animal model. In the hyt/hyt mouse primary hypothyroidism occurs due to a point mu tation in the beta subunit of the thyroid-stimulating hormone receptor of t he thyroid gland, and it is transmitted in an autosomal recessive manner. W e studied the effect of maternal betamethasone on fetal lung ultrastructure in hyt/hyt (hypothyroid) and Balb-c (euthyroid) mice. Hypothyroid mice wer e made euthyroid by T-3 supplementation and mated to carry hypothyroid pups . Vehicle (n = 6) or betamethasone (n = 6) was injected intraperitoneally t wice daily into the doe on days 16 and 17 of gestation. Fetal lungs on 18 d ays of gestation were subjected to ultrastructural morphometric analysis. T he number of lamellar bodies per type II cell increased after betamethasone in Balb-c (2.10 +/- 0.31 vs. 3.43 +/- 0.37) and hyt/hyt (0.77 +/- 0.28 vs. 3.85 +/- 0.26) mice. The alveolar-to-parenchymal ratio was less in the veh icle-treated hyt/hyt (0.082 +/- 0.024) as compared with the vehicle-treated Balb-c (0.30 +/- 0.05) mice, while prenatal betamethasone increased the al veolar-to-parenchymal ratio in the hyt/hyt (0.227 +/- 0.034) but not in the Balb-c (0.26 +/- 0.04) mice. The glycogen-to-nucleus ratio was higher in b etamethasone-treated hyt/hyt mice (1.46 +/- 0.20) when compared to vehicle- treated hyt/hyt (0.89 +/- 0.14) or Balb-c (1.01 +/- 0.17) or betamethasone- treated Balb-c (0.81 +/- 0.13) mice. Though tubular myelin was readily appa rent in the airspace lumen of betamethasone-treated Balb-c mice, it was abs ent in betamethasone-treated hyt/hyt fetal lungs. We conclude that fetal th yroid plays an important role in accelerating some aspects of fetal lung ul trastructural maturation from GC stimulation. Copyright (C) 2000 S. Karger AG, Basel.