Skip to main content
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1979 Jan-Feb;52(1):49–60.

The Role of Hepatotrophic Factors in Liver Regeneration — A Brief Review Including a Preliminary Report of the In Vitro Effects of Hepatic Regenerative Stimulator Substance (SS)

Douglas R Labrecque
PMCID: PMC2595718  PMID: 452622

Abstract

Details are presented of a technique for maintaining adult liver parenchymal cells in culture in a nonproliferating state. Hepatic regenerative stimulator substance (SS), prepared from weanling rat liver, will stimulate tritiated thymidine incorporation into liver DNA when injected into another rat or mouse. Preliminary experiments are presented which show that SS stimulates non-proliferating adult hepatocytes to incorporate increased amounts of 3HT dr into DNA when SS is added to the culture medium. The response is dose dependent and a lag period of about 12 hours exists between addition of SS to the cultures and the stimulation of DNA synthesis. Preliminary screening of several cell lines in culture reveals that only liver related cell lines (hepatomas) respond to SS. A brief review of other hepatotrophic factors is also included.

Full text

PDF
49

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BUCHER N. L. REGENERATION OF MAMMALIAN LIVER. Int Rev Cytol. 1963;15:245–300. doi: 10.1016/s0074-7696(08)61119-5. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbiroli B., Potter V. R. DNA synthesis and interaction between controlled feeding schedules and partial hepatectomy in rats. Science. 1971 May 14;172(3984):738–741. doi: 10.1126/science.172.3984.738. [DOI] [PubMed] [Google Scholar]
  4. Bissell D. M., Hammaker L. E., Meyer U. A. Parenchymal cells from adult rat liver in nonproliferating monolayer culture. I. Functional studies. J Cell Biol. 1973 Dec;59(3):722–734. doi: 10.1083/jcb.59.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonney R. J. Adult liver parenchymal cells in primary culture characteristics and cell recognition standards. In Vitro. 1974 Jul-Aug;10:130–142. doi: 10.1007/BF02615346. [DOI] [PubMed] [Google Scholar]
  6. Bucher M. L., Swaffield M. N. Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1157–1160. doi: 10.1073/pnas.72.3.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bucher N. L. Experimental aspects of hepatic regeneration. N Engl J Med. 1967 Oct 5;277(14):738–concl. doi: 10.1056/NEJM196710052771405. [DOI] [PubMed] [Google Scholar]
  8. Bucher N. L., Swaffield M. N. Regeneration of liver in rats in the absence of portal splanchnic organs and a portal blood supply. Cancer Res. 1973 Dec;33(12):3189–3194. [PubMed] [Google Scholar]
  9. Bucher N. L., Weir G. C. Insulin, glucagon, liver regeneration, and DNA synthesis. Metabolism. 1976 Nov;25(11 Suppl 1):1423–1425. doi: 10.1016/s0026-0495(76)80156-4. [DOI] [PubMed] [Google Scholar]
  10. Fisher B., Szuch P., Levine M., Fisher E. R. A portal blood factor as the humoral agent in liver regeneration. Science. 1971 Feb 12;171(3971):575–577. doi: 10.1126/science.171.3971.575. [DOI] [PubMed] [Google Scholar]
  11. GRISHAM J. W. A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Res. 1962 Aug;22:842–849. [PubMed] [Google Scholar]
  12. HARKNESS R. D. The spatial distribution of dividing cells in the liver of the rat after partial hepatectomy. J Physiol. 1952 Apr;116(4):373–379. doi: 10.1113/jphysiol.1952.sp004711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Howard R. B., Lee J. C., Pesch L. A. The fine structure, potassium content, and respiratory activity of isolated rat liver parenchymal cells prepared by improved enzymatic techniques. J Cell Biol. 1973 Jun;57(3):642–658. doi: 10.1083/jcb.57.3.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jeejeebhoy K., Phillips M. J. Isolated mammalian hepatocytes in culture. Gastroenterology. 1976 Dec;71(6):1086–1096. [PubMed] [Google Scholar]
  15. KELLY L. S., JONES H. B. Influence of homologous tissue factors on DNA turnover and radiation protection. Am J Physiol. 1953 Mar;172(3):575–578. doi: 10.1152/ajplegacy.1953.172.3.575. [DOI] [PubMed] [Google Scholar]
  16. Kuo C. Y., Yoo T. J. In vitro inhibition of tritiated thymidine uptake in Morris hepatoma cells by normal rat liver extract: a possible liver chalone. J Natl Cancer Inst. 1977 Dec;59(6):1691–1695. doi: 10.1093/jnci/59.6.1691. [DOI] [PubMed] [Google Scholar]
  17. LEONG G. F., GRISHAM J. W., HOLE B. V., ALBRIGHT M. L. EFFECT OF PARTIAL HEPATECTOMY ON DNA SYNTHESIS AND MITOSIS IN HETEROTOPIC PARTIAL AUTOGRAFTS OF RAT LIVER. Cancer Res. 1964 Sep;24:1496–1501. [PubMed] [Google Scholar]
  18. LaBrecque D. R., Bachur N. R., Peterson J. A., Howard R. B. The importance of the techniques employed during the enzymatic preparation of isolated liver parenchymal cells. J Cell Physiol. 1973 Dec;82(3):397–400. doi: 10.1002/jcp.1040820309. [DOI] [PubMed] [Google Scholar]
  19. LaBrecque D. R., Feigenbaum A., Bachur N. R. Diurnal rhythm: effects on hepatic regeneration and hepatic regenerative stimulator substance. Science. 1978 Mar 10;199(4333):1082–1084. doi: 10.1126/science.564547. [DOI] [PubMed] [Google Scholar]
  20. LaBrecque D. R., Howard R. B. The preparation and characterization of intact isolated parenchymal cells from rat liver. Methods Cell Biol. 1976;14:327–340. doi: 10.1016/s0091-679x(08)60493-8. [DOI] [PubMed] [Google Scholar]
  21. LaBrecque D. R., Pesch L. A. Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver. J Physiol. 1975 Jun;248(2):273–284. doi: 10.1113/jphysiol.1975.sp010973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lavigne J., Lalanne M., Thompson J. P., Simard A. Specific inhibition of the incorporation of tritiated thymidine in regenerating rat liver by a rat hepatocytes supernatant. Rev Can Biol. 1977 Mar;36(1):27–36. [PubMed] [Google Scholar]
  23. Leffert H. L., Paul D. Studies on primary cultures of differentiated fetal liver cells. J Cell Biol. 1972 Mar;52(3):559–568. doi: 10.1083/jcb.52.3.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MARCHIORO T. L., PORTER K. A., DICKINSON T. C., FARIS T. D., STARZI T. E. PHYSIOLOGIC REQUIREMENTS FOR AUXILIARY LIVER HOMOTRANSPLANTATION. Surg Gynecol Obstet. 1965 Jul;121:17–31. [PMC free article] [PubMed] [Google Scholar]
  25. Marchioro T. L., Porter K. A., Brown B. I., Faris T. D., Herrmann T. J., Sudweeks A., Starzl T. E. The specific influence of nonhepatic splanchnic venous blood flow on the liver. Surg Forum. 1965;16:280–282. [PMC free article] [PubMed] [Google Scholar]
  26. Marchioro T. L., Porter K. A., Brown B. I., Otte J. B., Starzl T. E. The effect of partial portacaval transposition on the canine liver. Surgery. 1967 May;61(5):723–732. [PMC free article] [PubMed] [Google Scholar]
  27. Max M. H., Price J. B., Takeshige K., Voorhees A. B., Jr The role of factors of portal origin in modifying hepatic regeneration. J Surg Res. 1972 Feb;12(2):120–123. doi: 10.1016/0022-4804(72)90131-x. [DOI] [PubMed] [Google Scholar]
  28. Miyamoto M., Terayama H. Nature of rat liver cell sap factors inhibiting the DNA synthesis in tumour cells. Biochim Biophys Acta. 1971 Jan 28;228(2):324–330. doi: 10.1016/0005-2787(71)90040-2. [DOI] [PubMed] [Google Scholar]
  29. Moolten F. L., Bucher N. L. Regeneration of rat liver: transfer of humoral agent by cross circulation. Science. 1967 Oct 13;158(3798):272–274. doi: 10.1126/science.158.3798.272. [DOI] [PubMed] [Google Scholar]
  30. Morley C. G., Kingdon H. S. The regulation of cell growth. I. Identification and partial characterization of a DNA synthesis stimulating factor from the serum of partially hepatectomized rats. Biochim Biophys Acta. 1973 May 10;308(2):260–275. doi: 10.1016/0005-2787(73)90156-1. [DOI] [PubMed] [Google Scholar]
  31. Morley C. G., Kingdon H. S. Use of 3 H-thymidine for measurement of DNA synthesis in rat liver--a warning. Anal Biochem. 1972 Jan;45(1):298–305. doi: 10.1016/0003-2697(72)90030-9. [DOI] [PubMed] [Google Scholar]
  32. Murison G. L. Growth of fetal rat liver cells in response to hydrocortisone. Exp Cell Res. 1976 Jul;100(2):439–443. doi: 10.1016/0014-4827(76)90177-4. [DOI] [PubMed] [Google Scholar]
  33. Otsuka H., Terayama H. Inhibition of DNA synthesis in ascites hepatoma cells by normal liver extract. Biochim Biophys Acta. 1966 Aug 17;123(2):274–285. doi: 10.1016/0005-2787(66)90280-2. [DOI] [PubMed] [Google Scholar]
  34. Price J. B., Jr Insulin and glucagon as modifiers of DNA synthesis in the regenerating rat liver. Metabolism. 1976 Nov;25(11 Suppl 1):1427–1428. doi: 10.1016/s0026-0495(76)80157-6. [DOI] [PubMed] [Google Scholar]
  35. SIGEL B., ACEVEDO F. J., DUNN M. R. The effect of patial hepatectomy on autotransplanted liver tissue. Surg Gynecol Obstet. 1963 Jul;117:29–36. [PubMed] [Google Scholar]
  36. STARZL T. E., MARCHIORO T. L., ROWLANDS D. T., Jr, KIRKPATRICK C. H., WILSON W. E., RIFKIND D., WADDELL W. R. IMMUNOSUPPRESSION AFTER EXPERIMENTAL AND CLINICAL HOMOTRANSPLANTATION OF THE LIVER. Ann Surg. 1964 Sep;160:411–439. doi: 10.1097/00000658-196409000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sakai A. Humoral factor triggering DNA synthesis after partial hepatectomy in the rat. Nature. 1970 Dec 19;228(5277):1186–1187. doi: 10.1038/2281186a0. [DOI] [PubMed] [Google Scholar]
  38. Sigel B., Baldia L. B., Dunn M. R., Menduke H. Humoral control of liver regeneration. Surg Gynecol Obstet. 1967 May;124(5):1023–1031. [PubMed] [Google Scholar]
  39. Sigel B., Baldia L. B., Menduke H., Feigl P. Independence of hyperplastic and hypertrhic responses in liver regeneration. Surg Gynecol Obstet. 1967 Jul;125(1):95–100. [PubMed] [Google Scholar]
  40. Starzl T. E., Francavilla A., Halgrimson C. G., Francavilla F. R., Porter K. A., Brown T. H., Putnam C. W. The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood. Surg Gynecol Obstet. 1973 Aug;137(2):179–199. [PMC free article] [PubMed] [Google Scholar]
  41. Starzl T. E., Porter K. A., Putnam C. W. Intraportal insulin protects from the liver injury of portacaval shunt in dogs. Lancet. 1975 Dec 20;2(7947):1241–1242. doi: 10.1016/s0140-6736(75)92076-0. [DOI] [PubMed] [Google Scholar]
  42. Starzl T. E., Watanabe K., Porter K. A., Putnam C. W. Effects of insulin, glucagon, and insuling/glucagon infusions on liver morphology and cell division after complete portacaval shunt in dogs. Lancet. 1976 Apr 17;1(7964):821–825. doi: 10.1016/s0140-6736(76)90477-3. [DOI] [PubMed] [Google Scholar]
  43. TEIR H., RAVANTI K. Mitotic activity and growth factors in the liver of the white rat. Exp Cell Res. 1953 Dec;5(2):500–507. doi: 10.1016/0014-4827(53)90236-5. [DOI] [PubMed] [Google Scholar]
  44. Verly W. G. The hepatic chalone. Natl Cancer Inst Monogr. 1973 Jul;38:175–184. [PubMed] [Google Scholar]
  45. WEINBREN K. Regeneration of the liver. Gastroenterology. 1959 Nov;37:657–678. [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES