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. 1977 Nov 1;75(2):398–409. doi: 10.1083/jcb.75.2.398

Glucocorticoids modulate the in vitro development of the embryonic rat pancreas

PMCID: PMC2109945  PMID: 264117

Abstract

The effect of the glucocorticoid analogue, dexamethasone, on the development of the embryonic pancreas was studied in tissue culture. It specifically enhances the accumulation of exocrine enzymes without altering the level of general cell proteins. The enhancement, however, is not symmetrical: the cellular levels of the two major exocrine products, amylase and chymotrypsinogen, are increased about 10- and 2- fold, respectively. Two other zymogens that are present in minor quantities, procarboxypeptidases A and B, are also increased, whereas no effect is seen on lipase A. Coordinate with these effects on synthesis, there is a dramatic change in the morphology of dexamethasone-stimulated acinar cells. Their number of zymogen granules is higher and crystalline arrays are found in the rough endoplasmic reticulum. Dexamethasone also inhibits cell replication, perhaps by selectively inhibiting the last cell divisions of the culture period. At the same time, there is a disproportionate reduction in the insulin content of cultured rudiments. We find that pancreatic development is normal in the absence of dexamethasone and that this glucocorticoid does not precociously induce the appearance of the specific secretory products, but rather enhances by a constant degree their synthesis and accumulation. Therefore, we conclude that glucocorticoids may play a modulatory but not an inductive role in pancreatic development.

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Selected References

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  1. Ballard P. L., Ballard R. A. Glucocorticoid receptors and the role of glucocorticoids in fetal lung development. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2668–2672. doi: 10.1073/pnas.69.9.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradshaw W. S., Rutter W. J. Multiple pancreatic lipases. Tissue distribution and pattern of accumulation during embryological development. Biochemistry. 1972 Apr 11;11(8):1517–1528. doi: 10.1021/bi00758a029. [DOI] [PubMed] [Google Scholar]
  3. Buckingham M. E., Caput D., Cohen A., Whalen R. G., Gros F. The synthesis and stability of cytoplasmic messenger RNA during myoblast differentiation in culture. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1466–1470. doi: 10.1073/pnas.71.4.1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clark W. R., Rutter W. J. Synthesis and accumulation of insulin in the fetal rat pancreas. Dev Biol. 1972 Dec;29(4):468–481. doi: 10.1016/0012-1606(72)90084-x. [DOI] [PubMed] [Google Scholar]
  5. Cohen A., Heller H., Kulka R. G. The effect of hydrocortisone on exportable enzyme accumulation in the differentiating chick pancreas. Dev Biol. 1972 Nov;29(3):293–306. doi: 10.1016/0012-1606(72)90069-3. [DOI] [PubMed] [Google Scholar]
  6. Cohen A. Plasma corticosterone concentration in the foetal rat. Horm Metab Res. 1973 Jan;5(1):66–66. [PubMed] [Google Scholar]
  7. Forssmann W. G., Bieger W. Biosynthese falscher Proteine: Einbau von p-Chlorphenylalanin in Enzyme des exokrinen Pankreas. Res Exp Med (Berl) 1973 Mar 14;160(1):1–20. doi: 10.1007/BF01852575. [DOI] [PubMed] [Google Scholar]
  8. Forssmann W. G., Bieger W., Roth H. Untersuchungen der falschen Proteinsynthese im exokrinen Pankreas. Verh Anat Ges. 1972;67:507–515. [PubMed] [Google Scholar]
  9. Giannopoulos G., Hassan Z., Solomon S. Glucocorticoid receptors in fetal and adult rabbit tissues. J Biol Chem. 1974 Apr 25;249(8):2424–2427. [PubMed] [Google Scholar]
  10. Greengard O., Dewey H. K. The premature deposition or lysis of glycogen in livers of fetal rats injected with hydrocortisone or glucagon. Dev Biol. 1970 Mar;21(3):452–461. doi: 10.1016/0012-1606(70)90135-1. [DOI] [PubMed] [Google Scholar]
  11. Henning S. J., Ballard P. L., Kretchmer N. A study of the cytoplasmic receptors for glucocorticoids in intestine of pre- and postweanling rats. J Biol Chem. 1975 Mar 25;250(6):2073–2079. [PubMed] [Google Scholar]
  12. Jones R. E., Moscona A. A. Effects of cytosine arabinoside on differential gene expression in embryonic neural retina. I. Accumulation of glutamine synthetase with suppression of macromolecular synthesis. J Cell Biol. 1974 Jun;61(3):688–700. doi: 10.1083/jcb.61.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. KAMOUN A., MIALHE-VOLOSS C., STUTINSKY F. EVOLUTION DE LA TENEUR EN CORTICOST'ERONE DE LA SURR'ENALE FOETALE DU RAT. C R Seances Soc Biol Fil. 1964;158:828–832. [PubMed] [Google Scholar]
  14. Kemp J. D., Walther B. T., Rutter W. J. Protein synthesis during the secondary developmental transition of the embryonic rat pancreas. J Biol Chem. 1972 Jun 25;247(12):3941–3952. [PubMed] [Google Scholar]
  15. Lin R. I., Schjeide O. A. Micro estimation of RNA by the cupric ion catalyzed orcinol reaction. Anal Biochem. 1969 Mar;27(3):473–483. doi: 10.1016/0003-2697(69)90061-x. [DOI] [PubMed] [Google Scholar]
  16. Lippman M. E., Wiggert B. O., Chader G. J., Thompson E. B. Glucocorticoid receptors. Characteristics, specificity, and ontogenesis in embryonic chick neural retina. J Biol Chem. 1974 Sep 25;249(18):5916–5917. [PubMed] [Google Scholar]
  17. Loeb J. N., Borek C., Yeung L. L. Suppression of DNA synthesis in hepatoma cells exposed to glucocorticoid hormone in vitro. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3852–3856. doi: 10.1073/pnas.70.12.3852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mills E. S., Topper Y. J. Some ultrastructural effects of insulin, hydrocortisone, and prolactin on mammary gland explants. J Cell Biol. 1970 Feb;44(2):310–328. doi: 10.1083/jcb.44.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moog F., Denes A. E., Powell P. M. Disaccharidases in the small intestine of the mouse: normal development and influence of cortisone, actinomycin D, and cycloheximide. Dev Biol. 1973 Nov;35(1):143–159. doi: 10.1016/0012-1606(73)90012-2. [DOI] [PubMed] [Google Scholar]
  20. Palmiter R. D. Quantitation of parameters that determine the rate of ovalbumin synthesis. Cell. 1975 Mar;4(3):189–189. doi: 10.1016/0092-8674(75)90167-1. [DOI] [PubMed] [Google Scholar]
  21. Pictet R. L., Clark W. R., Williams R. H., Rutter W. J. An ultrastructural analysis of the developing embryonic pancreas. Dev Biol. 1972 Dec;29(4):436–467. doi: 10.1016/0012-1606(72)90083-8. [DOI] [PubMed] [Google Scholar]
  22. Plas C., Chapeville F., Jacquot R. Development of glycogen storage ability under cortisol control in primary cultures of rat fetal hepatocytes. Dev Biol. 1973 May;32(1):82–91. doi: 10.1016/0012-1606(73)90221-2. [DOI] [PubMed] [Google Scholar]
  23. Rall L. B., Pictet R. L., Williams R. H., Rutter W. J. Early differentiation of glucagon-producing cells in embryonic pancreas: a possible developmental role for glucagon. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3478–3482. doi: 10.1073/pnas.70.12.3478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Reel J. R., Lee K. L., Kenney F. T. Regulation of tyrosine alpha-ketoglutarate transaminase in rat liver. 8. Inductions by hydrocortisone and insulin in cultured hepatoma cells. J Biol Chem. 1970 Nov 10;245(21):5800–5805. [PubMed] [Google Scholar]
  25. Reif-Lehrer L. Development of glutamine synthetase activity in chick embryo retina cultures in the absence of added hydrocortisone. Biochem Biophys Res Commun. 1968 Dec 30;33(6):984–989. [PubMed] [Google Scholar]
  26. Ronzio R. A., Rutter W. J. Effects of a partially purified factor from chick embryos on macromolecular synthesis of embryonic pancreatic epithelia. Dev Biol. 1973 Feb;30(2):307–320. doi: 10.1016/0012-1606(73)90091-2. [DOI] [PubMed] [Google Scholar]
  27. Sanders T. G., Rutter W. J. Molecular properties of rat pancreatic and parotid -amylase. Biochemistry. 1972 Jan 4;11(1):130–136. doi: 10.1021/bi00751a022. [DOI] [PubMed] [Google Scholar]
  28. Sanders T. G., Rutter W. J. The developmental regulation of amylolytic and proteolytic enzymes in the embryonic rat pancreas. J Biol Chem. 1974 Jun 10;249(11):3500–3509. [PubMed] [Google Scholar]
  29. Spooner B. S., Walther B. T., Rutter W. J. The development of the dorsal and ventral mammalian pancreas in vivo and in vitro. J Cell Biol. 1970 Oct;47(1):235–246. doi: 10.1083/jcb.47.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinberg R. A., Levinson B. B., Tomkins G. M. Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2007–2011. doi: 10.1073/pnas.72.6.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sugimoto M., Tajima K., Kojima A., Endo H. Differential acceleration by hydrocortisone of the accumulation of epidermal structural proteins in the chick embryonic skin growing in a chemically defined medium. Dev Biol. 1974 Aug;39(2):295–307. doi: 10.1016/0012-1606(74)90241-3. [DOI] [PubMed] [Google Scholar]

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