Development of the lung liquid reabsorptive mechanism in fetal sheep: synergism of triiodothyronine and hydrocortisone.

1. Thyroidectomy was performed on twelve fetal sheep between 111 and 115 days gestation. Measurement of fetal lung liquid secretion and absorption rates (Jv) were made at rest and during short (45 min) and long (5 h) infusions of adrenaline (0.5 micrograms/min) in a total of thirty-seven experiments, some in the absence of triiodothyronine (T3) and hydrocortisone and some at set times after the administration of the two hormones. 2. T3 was given either as an I.V. infusion (60 micrograms/24 h) or as a bolus of 30 micrograms; hydrocortisone was given as an infusion of 10 mg/24 h. Both hormones were administered together. 3. Before T3 and hydrocortisone were given short infusions of adrenaline had no effect on Jv but 4 h after exposure to the hormones secretion rate was reduced to near zero (Jv = -0.5 +/- 1.6 ml/h, n = 4) by adrenaline; after 24 h of hormone exposure, absorption of fetal lung liquid was produced by adrenaline (Jv = -3.6 +/- 2.2 ml/h, n = 4) which was even greater after 72 h, (Jv = -11.2 +/- 2.2 ml/h, n = 4). 4. During long infusions of adrenaline when T3 and hydrocortisone were given at the start of the experiment, an effect on lung liquid secretion was evident at 2 h and absorption was produced at 4 h (Jv = -4.2 +/- 2.5 ml/h, n = 3). The effect was significantly different from control long infusions of adrenaline performed the previous day in the absence of hormones. 5. After 24 or 48 h of stopping T3 and hydrocortisone administration, adrenaline no longer produced absorption of lung liquid, indicating that the effect of the two hormones was reversible within 24-48 h. 6. The protein synthesis inhibitor cycloheximide put into lung liquid (4 x 10(-5) to 3 x 10(-4) M) blunted the effect of the hormones at 4 h and prevented absorption of lung liquid at 24 h. Jv during adrenaline was -3.6 +/- 1.5 ml/h in control experiments but was +3.3 +/- 0.9 ml/h after cycloheximide, n = 4, P < 0.01. This indicated that the two hormones produced their effect through protein synthesis.