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. 1978 Aug 1;78(2):319–337. doi: 10.1083/jcb.78.2.319

Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age

PMCID: PMC2110128  PMID: 690169

Abstract

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) there are remarkable similarities in hepatocyte ultrastructure between very young and senescent animals, including cell size and the amount of SER.

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Selected References

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  1. ANDREW W. CHANGES IN THE NUCLEUS WITH ADVANCING AGE OF THE ORGANISM. Adv Gerontol Res. 1964;18:87–107. [PubMed] [Google Scholar]
  2. Adelman R. C. An age-dependent modification of enzyme regulation. J Biol Chem. 1970 Mar 10;245(5):1032–1035. [PubMed] [Google Scholar]
  3. Babcock M. B., Cardell R. R., Jr Hepatic glycogen patterns in fasted and fed rats. Am J Anat. 1974 Jul;140(3):299–337. doi: 10.1002/aja.1001400302. [DOI] [PubMed] [Google Scholar]
  4. Blouin A., Bolender R. P., Weibel E. R. Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study. J Cell Biol. 1977 Feb;72(2):441–455. doi: 10.1083/jcb.72.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burger P. C., Herdson P. B. Phenobarbital-induced fine structural changes in rat liver. Am J Pathol. 1966 May;48(5):793–809. [PMC free article] [PubMed] [Google Scholar]
  6. Castagna M., Chauveau J. Séparation des hépatocytes isolés de rat en fractions cellulaires métaboliquement distinctes. Exp Cell Res. 1969 Oct;57(2):211–222. doi: 10.1016/0014-4827(69)90143-8. [DOI] [PubMed] [Google Scholar]
  7. Coleman G. L., Barthold W., Osbaldiston G. W., Foster S. J., Jonas A. M. Pathological changes during aging in barrier-reared Fischer 344 male rats. J Gerontol. 1977 May;32(3):258–278. doi: 10.1093/geronj/32.3.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  9. Cooper A. D., Jones A. L., Koldinger R. E., Ockner R. K. Selective biliary obstruction: a model for the study of lipid metabolism in cholestasis. Gastroenterology. 1974 Apr;66(4):574–585. [PubMed] [Google Scholar]
  10. Drochmans P., Wanson J. C., Mosselmans R. Isolation and subfractionation on ficoll gradients of adult rat hepatocytes. Size, morphology, and biochemical characteristics of cell fractions. J Cell Biol. 1975 Jul;66(1):1–22. doi: 10.1083/jcb.66.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haining J. L., Legan J. S. Catalase turnover in rat liver and kidney as a function of age. Exp Gerontol. 1973 Apr;8(2):85–91. doi: 10.1016/0531-5565(73)90018-1. [DOI] [PubMed] [Google Scholar]
  12. Herbener G. H. A morphometric study of age-dependent changes in mitochondrial population of mouse liver and heart. J Gerontol. 1976 Jan;31(1):8–12. doi: 10.1093/geronj/31.1.8. [DOI] [PubMed] [Google Scholar]
  13. Hrůza Z., Zbuzková V. Decrease of excretion of cholesterol during aging. Exp Gerontol. 1973 Feb;8(1):29–37. doi: 10.1016/0531-5565(73)90048-x. [DOI] [PubMed] [Google Scholar]
  14. Jones A. L., Schmucker D. L., Mooney J. S., Adler R. D., Ockner R. K. Morphometric analysis of rat hepatocytes after total billary obstruction. Gastroenterology. 1976 Dec;71(6):1050–1060. [PubMed] [Google Scholar]
  15. Kato R., Takanaka A. Metabolism of drugs in old rats. I. Activities of NADPH-linked electron transport and drug-metabolizing enzyme systems in liver microsomes of old rats. Jpn J Pharmacol. 1968 Dec;18(4):381–388. doi: 10.1254/jjp.18.381. [DOI] [PubMed] [Google Scholar]
  16. Katz N., Teutsch H. F., Sasse D., Jungermann K. Heterogeneous distribution of glucose-6-phosphatase in microdissected periportal and perivenous rat liver tissue. FEBS Lett. 1977 Apr 15;76(2):226–230. doi: 10.1016/0014-5793(77)80157-9. [DOI] [PubMed] [Google Scholar]
  17. Knook D. L., Sleyster E. C. Lysosomal enzyme activities in parenchymal and nonparenchymal liver cells isolated from young, adult and old rats. Mech Ageing Dev. 1976;5(6):389–398. doi: 10.1016/0047-6374(76)90036-1. [DOI] [PubMed] [Google Scholar]
  18. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lin C., Chang J. Electron microscopy of albumin synthesis. Science. 1975 Oct 31;190(4213):465–467. doi: 10.1126/science.170682. [DOI] [PubMed] [Google Scholar]
  20. Loud A. V. A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol. 1968 Apr;37(1):27–46. doi: 10.1083/jcb.37.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ménard D., Penasse W., Drochmans P., Hugon J. S. Glucose-6-phosphatase heterogeneity within the hepatic lobule of the phenobarbital-treated rat. Histochemie. 1974 Mar 6;38(3):229–239. doi: 10.1007/BF00493121. [DOI] [PubMed] [Google Scholar]
  22. NOVIKOFF A. B. Cell heterogeneity within the hepatic lobule of the rat: staining reactions. J Histochem Cytochem. 1959 Jul;7(4):240–244. doi: 10.1177/7.4.240. [DOI] [PubMed] [Google Scholar]
  23. Onishi H., Tsukuda S., Hayashi Y., Ogawa N., Yajima G. Effects of cytochrome c on liver functions of old rats. Nat New Biol. 1972 Sep 20;239(90):84–86. doi: 10.1038/newbio239084a0. [DOI] [PubMed] [Google Scholar]
  24. Pieri C., ZS-Nagy I., Mazzufferi G., Giuli C. The aging of rat liver as revealed by electron microscopic morphometry--I. Basic parameters. Exp Gerontol. 1975;10(5):291–304. doi: 10.1016/0531-5565(75)90006-6. [DOI] [PubMed] [Google Scholar]
  25. Pieri C., Zs-Nagy I., Giuli C., Mazzufferi G. The aging of rat liver as revealed by electron microscopic morphometry-II. Parameters of regenerated old liver. Exp Gerontol. 1975;10(6):341–349. doi: 10.1016/0531-5565(75)90024-8. [DOI] [PubMed] [Google Scholar]
  26. Schlede E. Varying effect of phenobarbital on hepatic drug metabolism in rats of different ages. Naunyn Schmiedebergs Arch Pharmacol. 1974;282(3):311–315. doi: 10.1007/BF00501239. [DOI] [PubMed] [Google Scholar]
  27. Schmucker D. L. Age-related changes in hepatic fine structure: a quantitative analysis. J Gerontol. 1976 Mar;31(2):135–143. doi: 10.1093/geronj/31.2.135. [DOI] [PubMed] [Google Scholar]
  28. Schmucker D. L., Jones A. L., Mills E. S. Morphometric analysis of the ultrastructural changes in the liver of aging rats. J Gerontol. 1974 Sep;29(5):506–513. doi: 10.1093/geronj/29.5.506. [DOI] [PubMed] [Google Scholar]
  29. Schumucker D. L., Mooney J. S., Jones A. L. Age-related changes in the hepatic endoplasmic reticulum: a quantitative analysis. Science. 1977 Sep 2;197(4307):1005–1008. doi: 10.1126/science.887935. [DOI] [PubMed] [Google Scholar]
  30. Shamoto M. Age differences in the ultrastructure of hepatic cells of thyroxine-treated rats. J Gerontol. 1968 Jan;23(1):1–8. doi: 10.1093/geronj/23.1.1. [DOI] [PubMed] [Google Scholar]
  31. TAUCHI H., SATO T. Some micromeasuring studies of hepatic cells in senility. J Gerontol. 1962 Jul;17:254–259. doi: 10.1093/geronj/17.3.254. [DOI] [PubMed] [Google Scholar]
  32. Tate E. L., Herbener G. H. A morphometric study of the density of mitochondrial cristae in heart and liver of aging mice. J Gerontol. 1976 Mar;31(2):129–134. doi: 10.1093/geronj/31.2.129. [DOI] [PubMed] [Google Scholar]
  33. Tauchi H., Sato T., Kobayashi H. Effect of age on ultrastructural changes of cortisone treated mouse hepatic cells. Mech Ageing Dev. 1974 Nov-Dec;3(5-6):279–290. doi: 10.1016/0047-6374(74)90024-4. [DOI] [PubMed] [Google Scholar]
  34. Van Bezooijen C. F., Grell T., Knook D. L. The effect of age on protein synthesis by isolated liver parenchymal cells. Mech Ageing Dev. 1977 Jul-Aug;6(4):293–304. doi: 10.1016/0047-6374(77)90031-8. [DOI] [PubMed] [Google Scholar]
  35. Wanson J. C., Drochmans P., May C., Penasse W., Popowski A. Isolation of centrolobular and perilobular hepatocytes after phenobarbital treatment. J Cell Biol. 1975 Jul;66(1):23–41. doi: 10.1083/jcb.66.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weibel E. R., Stäubli W., Gnägi H. R., Hess F. A. Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morphometric data for rat liver. J Cell Biol. 1969 Jul;42(1):68–91. doi: 10.1083/jcb.42.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Welsh F. A. Changes in distribution of enzymes within the liver lobule during adaptive increases. J Histochem Cytochem. 1972 Feb;20(2):107–111. doi: 10.1177/20.2.107. [DOI] [PubMed] [Google Scholar]
  38. Wheatley D. N. Binucleation in mammalian liver. Studies on the control of cytokinesis in vivo. Exp Cell Res. 1972 Oct;74(2):455–465. doi: 10.1016/0014-4827(72)90401-6. [DOI] [PubMed] [Google Scholar]
  39. Wilson P. D. Enzyme changes in ageing mammals. Gerontologia. 1973;19(2):79–125. doi: 10.1159/000211964. [DOI] [PubMed] [Google Scholar]
  40. Wilson P. D., Franks L. M. The effect of age on mitochondrial ultrastructure. Gerontologia. 1975;21(2):81–94. doi: 10.1159/000212035. [DOI] [PubMed] [Google Scholar]
  41. Wisse E. An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. J Ultrastruct Res. 1970 Apr;31(1):125–150. doi: 10.1016/s0022-5320(70)90150-4. [DOI] [PubMed] [Google Scholar]
  42. van Bezooijen C. F., de Leeuw-Israel F. R., Hollander C. F. On the role of hepatic cell ploidy in changes in liver function with age and following partial hepatectomy. Mech Ageing Dev. 1973 Mar;1(5):351–356. doi: 10.1016/0047-6374(73)90041-9. [DOI] [PubMed] [Google Scholar]

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