To investigate the possible mechanism of thyroid hormone action in the lung, we examined fetal and adult rabbit lung, and cell lines derived from lung, for specific nuclear binding sites for T3. Using incubation of isolated nuclei with L-[125I]T3 at 37 C, we found approximately 2400 specific binding sites/cell in fetal lung and 1120 sites/cell in adult lung, with a similar dissociation constant (approximately 500 pm) for both tissues. The L-2 and A549 cell lines, which may have originated from pulmonary type II alveolar cells, contained 2280 and 1580 nuclear sites/cell, and the dissociation constants were 280 and 200 pm, respectively. In fetal lung, the ability of various analogs to compete for L-T3 (100%) binding was: 3,5-diiodo-3'-isopropylthyronine, 81%; D-T3, 73%; L-T4, 6.7%; 3,3'-diiodothyronine, 0.19%; 3,5-dimethyl-3'-isopropyl-L-thyronine, 0.15%; and rT3, 0.08%. These findings indicate that both fetal and adult lung, and cultured lung cells, contain specific nuclear binding sites for T3, suggesting that these tissues and their type II alveolar cells may be directly influenced by thyroid hormones.

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To investigate the possible mechanism of thyroid hormone effects in lung development and function, we examined rabbit lung and two cell lines apparently derived from type I1 alveolar cells for specific nuclear binding of L-triiodothyronine (T3). Nuclei isolated from lung were incubated at 37 C for 1.5 h with various concentrations of [125~]-~3 in the presence and absence of excess non-labelled Tj, and then washed in buffer with 0.2% Triton X-100. In fetal lung, the concentration of T3 binding sites and the dissociation constant (Kd) were constant between 24-30 days gestation with mean*^^ values (n=17) of 0.67f0.05 fmollug DNA (2400 sites/cell) and 500f52 pM, respectively. Adult lung (n=3) bound 0.31f0.03 fmol T3/ug DNA (1120 siteslcell, p a l vs. fetal) and the Kd = 540f144 pM (NS). The L2 and A549 cell lines contained 2280 and 1580 nuclear siteslcell, and had Kd values of 200 and 280 pM, respectively. In fetal lung, the abil ity of analogs to compete for L-T3 binding (100%) was: 3,5-diiodo-3'-isopropylthyronine 81%, D-T3 73%, L-T4 6.7%. L-T2 0.19%, 3,5-dimethyl-3'-isopropyltbyronine 0.15%, and reverse T3 0.08%.We conclude that rabbit lung and cultured epithelial lung cells contain nuclear binding sites with a high affinity and specificity for thyroid hormones. This suggests that both fetal and adult lung and their type I1 cells may be directly influenced by these hormones. To determine the efficiency of conversion as a function of dose, relative amount of the biologically active metabolite of cortisone (E), hydrocortisone (F), available in systemic circulation was determined following the oral administration of 5 and 50 mg of E containing 1 to 6 uc 14C-E. 26 studies were done: 8 dell subjects; 7 children, adrenogenital syndrome; 5, growth hormo:re deficiency; 2, Crohn's disease. Plasma concentrations of F were determined by liquid scintillation counting following TLC separation using silica ge? HF-254 and a solvent system of methylene chloride-ethanal (90-10). Relative fraction of F which reaches the systemic circulation was estimated by using the area ~nder the plasma concentration time curve normalized for differences in the radioactive dose and surface area of the subject. (AUC'). AUC' values of F for 50 mg E given i.v. is only slightly greater than when 50 mg E was given orally, but the F to E ratio vas much greater by the oral route indicating a greater preponjerance of the E to F conversion pathway during the absorptive ~hase. Mean normalized AUC values (in units of percent radiolctive dose, liter-1, min.) for 5 and 50 mg dose were 283.5 SDt104.7) and 157.8 (SD30.6) respectively, (p-