Quantitative stereological methods have been adapted for the measurement of the volume of liver attributable to parenchymal, hematopoietic, and Kupffer cells and for the measurement of the relative and absolute number (per unit volume) of these cell types and the mean volume of the parenchymal cell. These morphological parameters are the main ones for interpreting the biochemical differentiation of liver. Quantitative changes in these parameters, in rat liver between the 15th day of gestation and adult life, are presented. Despite the large number of hematopoietic cells, the parenchymal cells fill more than half of the liver volume between the 15th and 18th days of gestation and 0.85 of the liver volume at term. The fraction of liver volume occupied by Kupffer cells is never more than 0.02; the number of Kupffer cells per cubic centimeter increases less than twofold between fetal and adult life. The mean volume of individual parenchymal cells undergoes a threefold rise during late fetal life, declines in the neonatal period, and doubles between the 12th and 28th postnatal days. With the morphometric data obtained, it is impossible to convert enzyme concentrations (units per gram, determined in homogenates of whole liver) to enzyme amounts per unit volume of parenchymal or hematopoietic tissue or per individual cell of either type. In late fetal liver, only rises in enzyme concentration less than twofold may be attributed to the enrichment of parenchymal tissue at the expense of hematopoietic elements. The sudden upsurge, by more than twofold, of hepatic enzymes of the late fetal cluster (and also of the neonatal and late suckling cluster) reflects rises per parenchymal mass and per parenchymal cell. Thyroxine and glucagon, the administration of which to fetal rats promotes enzyme differentiation in liver, are without appreciable effect on the cytological parameters studied. Hydrocortisone accelerates the involution of hematopoietic tissue in fetal liver. Enzymes that are diminished by prenatal injection of hydrocortisone may be concentrated in hematopoietic cells.

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