Hydrocortisone promotes the maturation of Na(+)-dependent ion transport across the fetal pulmonary epithelium.
The pulmonary epithelium's change from Cl(-)-dependent fluid secretion to Na(+)-dependent fluid absorption in late gestation appears to be important in the transition of the lung from a fluid-filled organ in utero to an air-filled organ after birth. This maturational process may be regulated in part by hormones. We examined the effects of hydrocortisone on ion transport across monolayer cultures of distal pulmonary epithelial cells isolated from the fetal rat. Hydrocortisone pretreatment enhanced terbutaline (10(-5) M) stimulation of short-circuit current (Isc) but only in monolayers derived from immature fetal cells (day 18 of gestation), stimulating basal Isc by 270% in control monolayers and by 329% in hydrocortisone-pretreated monolayers. Amiloride (10(-4) M) inhibited terbutaline-stimulated Isc by different amounts, depending on gestational age and pretreatment; Isc fell 40% in control monolayers derived from immature cells, 68% in hydrocortisone-pretreated monolayers from immature fetal cells, and approximately 70% in both control and hydrocortisone-pretreated monolayers from mature fetal cells (day 21 of gestation). The basal Isc in monolayers derived from immature cells was also variably inhibited by amiloride with Isc decreasing 26% in control monolayers and 57% in hydrocortisone-pretreated monolayers. The differential responses of terbutaline-stimulated Isc to benzamil, dimethylamiloride, and bumetanide suggested that Isc sensitivity to amiloride was dependent predominantly on Na+ channel activity regardless of gestational age or pretreatment. We conclude that hydrocortisone promotes the maturation of transepithelial Na+ transport in fetal rat lung epithelium by altering Na+ entry into the cell through Na+ channels. Hydrocortisone also enhances beta-adrenergic agonist stimulation of ion transport.
Cott
G R
GR
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Rao
A K
AK
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus; D006854:Hydrocortisone / Q000502:physiology*; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008564:Membrane Potentials; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology
D012964:Sodium; D013726:Terbutaline; D006854:Hydrocortisone