Quantitative analysis of smooth and rough endoplasmic reticulum proliferation in differentiating hepatocytes of midpostnatal mice treated with phenobarbital.

The increase, expressed as a percentage of the control value, in the area of smooth endoplasmic reticulum (ER) per unit cytoplasmic volume did not differ between periportal and perivenular hepatocytes in 10-day-old mice injected with 50 mg/kg phenobarbital (PB) at 7, 8, and 9 days of age, whereas it was greater in perivenular than in periportal hepatocytes in 20-day-old animals injected with 100 mg/kg at 17, 18, and 19 days of age. Unexpectedly, the amount of rough ER increased after PB administration in both perivenular and periportal hepatocytes in the two age groups. Experiments done to determine the significance of the rough ER proliferation brought the following results. The intensity of immunohistochemical fluorescence for albumin decreased in both periportal and perivenular hepatocytes from 20-day-old animals treated with PB. NADPH-cytochrome c reductase activity increased in both smooth and rough microsomes in 20-day-old animals treated with PB. These results show that the predominant proliferation of smooth ER in perivenular hepatocytes after PB administration, characteristic of adult liver, arises between 10 and 20 days of age, and that rough ER proliferation, which is related to the increase in drug metabolism, is characteristic of the liver of midpostnatal mice.