Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1,6,10,16,20,25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume.The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) J. CELL BIOLOGY 9 The Rockefeller University Press 9

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The ultrastructural changes in hepatocytes of rats subjected to selective biliary obstruction (SBO), wherein the biliary system draining approximately two-thirds of the liver is obstructed, were evaluated by quantitative electron microscopy or stereology. The remaining unobstructed portion of the organ compensates for this loss of bile secretion by functioning in a hypersecretory mode. This animal model permits the comparison of hepatocellular fine structure associated with the conditions of nonsecretion and hypersecretion of bile with that found in normal secreting sham-operated rats. Since recent evidence suggests the presence of lobular gradients in hepatic structure and function, both centrolobular and periportal hepatocytes were examined. The low incidence of Golgi membrane profiles in high magnification electron micrographs results in a low confidence level of sampling and, thus, necessitates the application of a novel parameter for estimating the amount of Golgi complex, i.e., the Golgi-rich area. For the most part, the lobular variation in hepatic fine structure in the sham-operated animals was similar to that described by Loud ('68). However, the periportal parenchyma contained approximately twice the volume of Golgi-rich area as the centrolobular tissue. The amount of cytoplasmic lipid increased significantly in the SBO unobstructed lobes, although there were few or no changes in the other intracellular organelles or inclusions except those related to the Golgi complex. The volume of Golgi-rich area increased significantly in the centrolobular tissue of the SBO unobstructed (hypersecretory) lobes to the extent that both intralobular zones contained similar amounts of this component. These data suggest that the Golgi complex is a dynamic unit which responds to changes in hepatocellular activity and may be involved in bile secretion.

Morphometric analysis demonstrated a twofold increase in the surface area of the hepatic endoplasmic reticulum in Fischer 344 rats between 1 and 20 months of age, followed by a significant decrease in this parameter between 20 and 30 months. These changes are attributed to the smooth-surfaced endoplasmic reticulum, since neither the rough-surfaced variety nor the Golgi membranes underwent any significant change in surface area as a function of the age of the animal.