Influence of growth hormone on the lung growth response to tracheal obstruction in fetal sheep

Obstructing the fetal trachea is a potent stimulus for fetal lung growth, b ut little is known about the factors that regulate this process. Our aim wa s to determine the role of growth hormone (GH) in regulating the increase i n lung growth induced by obstruction of the trachea in fetal sheep. Twenty chronically catheterized fetal sheep, nine of which were hypophysectomized, were divided into:four experimental groups: I) control group (n = 4), 2) a group in which the fetal trachea was obstructed for 3 days (3-day obstruct ed; n = 6), 3) a 3-day obstructed group in which the pituitary was removed [hypophysectomized (HX)] and the fetus was given maintenance infusions of A CTH, thyroxine, and human GH (hGH; HX hGH 3-day obstructed; n = 5), and 4) a HX 3-day obstructed group in which the fetus was given maintenance infusi ons of ACTH and thyroxine (n = 5). Tracheal obstruction significantly incre ased fetal lung liquid volumes from 37.2 +/- 3.2 ml/kg in control fetuses t o 75.6 +/- 9.0 ml/kg in S-day obstructed fetuses, and the presence or absen ce of GH did not affect this increase. Similarly, the presence or absence o f GH did not affect the increase in lung weight or protein content induced by 3 days of tracheal obstruction. However, in the absence of GH, 3 days of tracheal obstruction failed to increase total lung DNA content above unobs tructed control values (107.9 +/- 5.3 and 94.1 +/- 7.0 mg/kg for control an d HX 3-day obstructed groups, respectively). In contrast, 3 days of trachea l obstruction increased total lung DNA content to a similar extent in fetus es with an intact pituitary and HX fetuses that received GH replacement (12 6.0 +/- 4.4 and 126.7 +/- 4.0 mg/kg for 3-day obstructed and HX hGH 3-day o bstructed groups, respectively). These data indicate that the absence of GH either abolishes or delays the acceleration in cell division caused by an increase in fetal lung expansion.