A B S T R A C T The effect of thyroid hormone on maturation of fetal rabbit lung was studied with maternal treatment using 3,5-dimethyl-3'-isopropyl-Lthyronine (DIMIT), a synthetic analogue of triiodothyronine. To investigate the in vivo kinetics and distribution of DIMIT, we prepared [3H]DIMIT and injected both pregnant rats (18-21 d gestation) and rabbits (25 d gestation). In the rat, maximal concentrations of radioactivity in maternal plasma, fetal plasma, and amniotic fluid occurred within 10 min, 1-2 h, and 4-6 h, respectively, after intramuscular injection. After 7 h the concentration of radioactivity in fetal plasma was 163 and 71% of the maternal level in rats and rabbits, respectively, indicating that DIMIT readily crosses the placenta.We treated pregnant rabbits for 1-2 d with DIMIT in doses of 0.5-3 mg/kg per d and examined the fetuses at 26 and 27 d gestation. Treatment did not affect fetal growth or viability. In fetal liver, DIMIT increased the activity of NADPH cytochrome c reductase by 64% and decreased the glycogen content by 73% compared to controls. The rate of choline incorporation by lung minces increased in a dose-dependent manner to a maximum of +104% at 3 mg/kg DIMIT; this dose stimulated by 38% the activity of lung phosphatidic acid phosphatase (PAPase), a corticosteroid-responsive enzyme, but there was no increase in tissue PAPase activity at most lower doses of DIMIT that enhanced choline incorporation. Treated lungs had 38% less glycogen than controls, but there was no effect on tissue levels of DNA, protein, or phospholipid. DIMIT treatment increased the amount of total phospholipid (+ 163%), saturated phosphatidylcholine (+330%), and PAPase activity (+ 134%) in lung lavage fluid. The DIMIT effects on both choline incorporation by lung A preliminary report of some of these results has been published (1).

The effects of an analog of thyroxine, 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), on fetal rat hepatocyte ultrastructure and microsomal function were investigated by using the techniques of quantitative electron microscopy and enzyme assays. Rats were injected with DIMIT (10 microgram/100 g BW) or vehicle daily from the 15th through the 19th day of pregnancy. Fetuses were sacrificed on the 20th day of gestation. In comparison with controls, DIMIT-treated livers 1) were devoid of glycogen; 2) contained smaller hepatocytes; 3) contained a greater number of hepatocytes; 4) had an increased volume density of mitochondria; and 5) had increased NADPH-cytochrome c reductase and glucose-6-phosphatase activities. Surface areas of rough and smooth surfaced endoplasmic reticulum were unaffected by the hormone analog, and cytochrome P-450 was not induced. All of the changes that were produced by DIMIT in the 20-day-old fetal rat, as well as smooth endoplasmic reticulum and cytochrome P-450 development, are observed in normal animals within the first 3 days after birth. The data suggest that thyroid hormone may be a physiological stimulus for certain aspects of early hepatic development, but that it acts in combination or in sequence with other factor(s) to produce the full complement of structural and functional changes that occur perinatally in the rat.

Electron microscope autoradiographs were prepared from diabetic rat pancreatic acini that had been incubated with 125I-insulin. Distribution histograms of the distance of the 125I-insulin silver grains from the nearest plasma membrane were prepared and compared with a histogram of an 125I line source. After 3 min of incubation, insulin was located predominately on the plasma membrane, but even at this early time 15% of the grains had an intracellular location. After 30 min of incubation, there was a decrease in grains on the plasma membrane and an increase (to 45%) in grains localized in the cell. At both times of incubation, a comparison of the distribution of the insulin grains overlying subcellular organelles to a theoretical random grain distribution pattern indicated that the intracellular distribution of insulin grains was nonrandom. At 3 min, there was a relative concentration of grains over the plasma membrane and vesicles with an average diameter of 100 nm. At 30 min, there was a concentration of grains over the plasma membrane, 100-nm vesicle, and Golgi. These studies suggest that 125I-insulin is internalized into pancreatic acinar cells in a time-dependent manner and then is nonrandomly distributed inside the cell.

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