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Selective Regulation of Gene Expression in the Exocrine Pancreas

George A. Scheele, Horst F. Kern

10.1002/cphy.cp060325

Source: Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Differential Regulation of Gene Expression
1.1 Separation of Gene Products by Two‐Dimensional Gel Electrophoresis
1.2 Adaptation to Inverse Changes in Nutritional Substrates in the Diet
1.3 Response to Hormonal Stimulation
1.4 Pavlov's Dietary Adaptation is Mediated by Specific Hormones
1.5 Nutritional Shock
2 Gene Expression Is Regulated At Multiple Levels
2.1 Prenatal and Postnatal Development
2.2 Nutritional Substrates and Hormones
3 Mechanisms in Selective Regulation of Gene Transcription
3.1 Processing Signals in Eucaryotic Genes
3.2 Promoter Elements
3.3 Enhancer Elements
4 Selective Regulation of Mrna Translation Efficiency: Possible Mechanisms
Figure 1. Figure 1.

Separation of gene products in the rat pancreas by 2‐dimensional gel electrophoresis. Proteins that are identified by actual or potential enzyme activity are labeled by abbreviations that are identified in Table 1. Numbers 1–4, unidentified proteins. P23, present after hormonal stimulation 70, does not appear by Coomassie blue stain among proteins collected under basal conditions. Ordinate, apparent Mr × 10−3. Abscissa, isoelectric points. Enzymes and zymogens are numbered consecutively from anode to cathode, following the recommendations of the IUPAC‐IUB Commission on the biochemical nomenclature of multiple forms of enzymes separated by polyacrylamide gel electrophoresis 2.
Figure 2. Figure 2.

Differential changes in synthesis of exocrine pancreatic proteins in response to reciprocal changes in carbohydrate and protein in the diet. After administration of isocaloric diets for 12 days, animals were sacrificed and rates of protein synthesis were measured by in vitro incorporation of a mixture of 15 14C‐labeled amino acids into pancreatic lobules followed by analysis of individual proteins after their separation by 2‐dimensional isoelectric focusing and sodium dodecyl sulfate gel electrophoresis.

From Scheele 65
Figure 3. Figure 3.

Differential changes in the synthesis of exocrine proteins in response to hormonal stimulation in the rat. Caerulein, a peptide analogue of CCK, was infused into the tail vein of conscious rats at a rate of 0.25 μg · kg−1 · h−1 for up to 24 h. Animals were sacrificed at indicated times, and protein synthesis rates were measured in absence of caerulein (see Fig. 2.

From Scheele 65
Figure 4. Figure 4.

Changes in the synthesis of pancreatic lipase in response to secretin stimulation in the rat. Secretin at 16 CU · kg−1 · h−1 (solid triangles), caerulein at 0.25 μg · kg−1 · h−1 (closed circles), and saline (open circles) were infused for up to 24 h. Animals were sacrificed at indicated times, and protein synthesis rates were measured (see Fig. 2.

From Rausch et al. 55
Figure 5. Figure 5.

Adaptation in the synthesis of exocrine proteins to dietary changes mediated by alterations in mRNA levels. Diets I‐V (with compositions indicated in Fig. 2 were administered for 8 days. A: fluorogram of exocrine protein products synthesized in intact pancreatic cells. B: fluorogram of protein products synthesized by isolated mRNA in a rabbit reticulocyte in vitro translation system, a study that measures functional levels of mRNA. Synthesis of individual proteins in intact cells (A) is proportional to functional levels of mRNA (B). A, amylase; L, lipase; PCP, procarboxypeptidases A and B; SP, serine proteases (including trypsinogen, chymotrypsinogen, and proelastase). Presecretory proteins demonstrating small increases in molecular‐weight values are synthesized during in vitro translation in the absence of microsomal membranes.

From Wicker et al. 92
Figure 6. Figure 6.

Absence of kinetic changes in concentrations of mRNA coding for rat pancreatic proteins, anionic trypsinogen, lipase, and amylase, during a single period of caerulein infusion. Hormone was infused at 0.25 μg · kg−1 · h−1 for up to 24 h. Messenger RNA concentrations were measured with nick‐translated cDNA probes on nitrocellulose dot blots. Measurements were made on pancreatic tissue taken from hormone‐infused (closed symbols) or saline‐infused (open symbols) animals and normalized to a standard sample of pancreatic RNA obtained from a group of noninfused animals; 3–4 animals were studied at each time point. Vertical bars, standard deviation values. Hatched areas, 1 standard deviation obtained in the measurement of the standard sample of RNA. Ordinate, values are given on a logarithmic scale. (W. Steinhilber, J. Poensgen, U. Rausch, H. Kern, and G. A. Scheele, unpublished observations.)
Figure 7. Figure 7.

Nucleotide signals involved in gene transcription and mRNA translation in the exocrine pancreas. Schematic depiction of a pancreatic gene shown without introns. Nomenclature for nucleotide signals is given directly above each sequence. Dashes, absence of nucleotide preference in consensus sequences. Putative tissue‐specific enhancer is taken from ref. 9.
Figure 8. Figure 8.

Conserved sequences at 5’ termini of mRNAs encoding pancreatic anionic trypsinogen and amylase. Vertical lines, identities. Dash in dog amylase mRNA sequence is introduced as a deletion to maximize sequence alignments. AUG initiation codons are underlined. Brackets, complementary sequences that may base‐pair to form stem‐loop structures. Anionic trypsinogen mRNA sequences from the rat 39 and dog 51; amylase mRNA sequences from the mouse 69, rat 38, and dog. (K. S. LaForge and G. A. Scheele, unpublished observations.)
Figure 9. Figure 9.

Potential function of the stem‐loop structure at the 3’ end of 18S ribosomal RNA (rRNA) as a molecular switch responsible for differential regulation of trypsinogen mRNA translation 51,65. The 5’ nontranslated region of cationic trypsinogen mRNA contains 5 contiguous nucleotides that show potential base‐pairing with the single‐stranded 3'‐terminal sequence of 18S rRNA. In contrast, the 5’ nontranslated region of anionic trypsinogen mRNA contains a conserved region in which 9 out of 10 nucleotides show potential hybridization largely to the left arm of the double‐stranded rRNA (stem) structure. Development of an open configuration in the stem‐loop sequence would have little effect on potential interactions with cationic trypsinogen mRNA but would allow extensive interactions with anionic trypsinogen mRNA, which could promote the alignment of mRNA during initiation of mRNA translation.


Figure 1.

Separation of gene products in the rat pancreas by 2‐dimensional gel electrophoresis. Proteins that are identified by actual or potential enzyme activity are labeled by abbreviations that are identified in Table 1. Numbers 1–4, unidentified proteins. P23, present after hormonal stimulation 70, does not appear by Coomassie blue stain among proteins collected under basal conditions. Ordinate, apparent Mr × 10−3. Abscissa, isoelectric points. Enzymes and zymogens are numbered consecutively from anode to cathode, following the recommendations of the IUPAC‐IUB Commission on the biochemical nomenclature of multiple forms of enzymes separated by polyacrylamide gel electrophoresis 2.



Figure 2.

Differential changes in synthesis of exocrine pancreatic proteins in response to reciprocal changes in carbohydrate and protein in the diet. After administration of isocaloric diets for 12 days, animals were sacrificed and rates of protein synthesis were measured by in vitro incorporation of a mixture of 15 14C‐labeled amino acids into pancreatic lobules followed by analysis of individual proteins after their separation by 2‐dimensional isoelectric focusing and sodium dodecyl sulfate gel electrophoresis.

From Scheele 65


Figure 3.

Differential changes in the synthesis of exocrine proteins in response to hormonal stimulation in the rat. Caerulein, a peptide analogue of CCK, was infused into the tail vein of conscious rats at a rate of 0.25 μg · kg−1 · h−1 for up to 24 h. Animals were sacrificed at indicated times, and protein synthesis rates were measured in absence of caerulein (see Fig. 2.

From Scheele 65


Figure 4.

Changes in the synthesis of pancreatic lipase in response to secretin stimulation in the rat. Secretin at 16 CU · kg−1 · h−1 (solid triangles), caerulein at 0.25 μg · kg−1 · h−1 (closed circles), and saline (open circles) were infused for up to 24 h. Animals were sacrificed at indicated times, and protein synthesis rates were measured (see Fig. 2.

From Rausch et al. 55


Figure 5.

Adaptation in the synthesis of exocrine proteins to dietary changes mediated by alterations in mRNA levels. Diets I‐V (with compositions indicated in Fig. 2 were administered for 8 days. A: fluorogram of exocrine protein products synthesized in intact pancreatic cells. B: fluorogram of protein products synthesized by isolated mRNA in a rabbit reticulocyte in vitro translation system, a study that measures functional levels of mRNA. Synthesis of individual proteins in intact cells (A) is proportional to functional levels of mRNA (B). A, amylase; L, lipase; PCP, procarboxypeptidases A and B; SP, serine proteases (including trypsinogen, chymotrypsinogen, and proelastase). Presecretory proteins demonstrating small increases in molecular‐weight values are synthesized during in vitro translation in the absence of microsomal membranes.

From Wicker et al. 92


Figure 6.

Absence of kinetic changes in concentrations of mRNA coding for rat pancreatic proteins, anionic trypsinogen, lipase, and amylase, during a single period of caerulein infusion. Hormone was infused at 0.25 μg · kg−1 · h−1 for up to 24 h. Messenger RNA concentrations were measured with nick‐translated cDNA probes on nitrocellulose dot blots. Measurements were made on pancreatic tissue taken from hormone‐infused (closed symbols) or saline‐infused (open symbols) animals and normalized to a standard sample of pancreatic RNA obtained from a group of noninfused animals; 3–4 animals were studied at each time point. Vertical bars, standard deviation values. Hatched areas, 1 standard deviation obtained in the measurement of the standard sample of RNA. Ordinate, values are given on a logarithmic scale. (W. Steinhilber, J. Poensgen, U. Rausch, H. Kern, and G. A. Scheele, unpublished observations.)



Figure 7.

Nucleotide signals involved in gene transcription and mRNA translation in the exocrine pancreas. Schematic depiction of a pancreatic gene shown without introns. Nomenclature for nucleotide signals is given directly above each sequence. Dashes, absence of nucleotide preference in consensus sequences. Putative tissue‐specific enhancer is taken from ref. 9.



Figure 8.

Conserved sequences at 5’ termini of mRNAs encoding pancreatic anionic trypsinogen and amylase. Vertical lines, identities. Dash in dog amylase mRNA sequence is introduced as a deletion to maximize sequence alignments. AUG initiation codons are underlined. Brackets, complementary sequences that may base‐pair to form stem‐loop structures. Anionic trypsinogen mRNA sequences from the rat 39 and dog 51; amylase mRNA sequences from the mouse 69, rat 38, and dog. (K. S. LaForge and G. A. Scheele, unpublished observations.)



Figure 9.

Potential function of the stem‐loop structure at the 3’ end of 18S ribosomal RNA (rRNA) as a molecular switch responsible for differential regulation of trypsinogen mRNA translation 51,65. The 5’ nontranslated region of cationic trypsinogen mRNA contains 5 contiguous nucleotides that show potential base‐pairing with the single‐stranded 3'‐terminal sequence of 18S rRNA. In contrast, the 5’ nontranslated region of anionic trypsinogen mRNA contains a conserved region in which 9 out of 10 nucleotides show potential hybridization largely to the left arm of the double‐stranded rRNA (stem) structure. Development of an open configuration in the stem‐loop sequence would have little effect on potential interactions with cationic trypsinogen mRNA but would allow extensive interactions with anionic trypsinogen mRNA, which could promote the alignment of mRNA during initiation of mRNA translation.

References
 1. Adler, G., and H. F. Kern. Regulation of exocrine pancreatic secretory process by insulin in vivo. Horm. Metab. Res. 7: 290–296, 1975.
 2. Anonymous. Nomenclature of multiple forms of enzymes. Eur. J. Biochem 82: 1–3, 1978.
 3. Banerji, J., L. Olson, and W. Schaffner. A lymphocyte‐specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33: 729–740, 1983.
 4. Bell, G., C. Quinto, M. Quiroga, P. Valenzuela, C. Craik, and W. Rutter. Isolation and sequence of a rat chymotrypsinogen B gene. J. Biol. Chem. 259: 14265–14270, 1984.
 5. Benne, R., and J. W. B. Hershey. Purification and characterization of initiation factor IF‐E3 from rabbit reticulocytes. Proc. Natl. Acad. Sci. USA 73: 3005–3009, 1976.
 6. Benne, R., C. Wong, M. Luedi, and J. W. B. Hershey. Purification and characterization of initiation factor IF‐E2 from rabbit reticulocytes. J. Biol. Chem. 251: 7675–7681, 1976.
 7. Benoist, C., K. O'Hare, R. Breathnach, and P. Chambon. The ovalbumin gene‐sequence of putative control regions. Nucleic Acids Res. 8: 127–142, 1980.
 8. Berget, S., C. Moore, and P. A. Sharp. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. USA 74: 3171–3175, 1977.
 9. Boulet, A. M., C. R. Erwin, and W. J. Rutter. Cell‐specific enhancers in the rat exocrine pancreas. Proc. Natl. Acad. Sci. USA 83: 3599–3603, 1986.
 10. Cato, A. C., R. Miksicek, G. Schütz, J. Arnemann, and M. Beato. The hormone regulatory element of mouse mammary tumor virus mediates progesterone induction. EMBO J. 5: 2237–2240, 1986.
 11. Chang, A., and J. D. Jamieson. Stimulus‐secretion coupling in the developing exocrine pancreas: secretory responsiveness to cholecystokinin. J. Cell Biol. 103: 2353–2365, 1986.
 12. Chow, L. T., R. E. Gelinas, T. R. Broker, and R. J. Roberts. An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA. Cell 12: 1–8, 1977.
 13. Craik, C., Q. Choo, G. Swift, C. Quinto, R. MacDonald, and W. Rutter. Structure of two related rat pancreatic trypsin genes. J. Biol. Chem. 259: 14255–14264, 1984.
 14. Dagorn, J. C., and R. G. Lahaie. Dietary regulation of pancreatic protein synthesis. I. Rapid specific modulation of enzyme synthesis by changes in dietary composition. Biochim. Biophys. Acta 654: 111–118, 1981.
 15. Dagorn, J. C., and R. Mongeau. Different action of hormonal stimulation on the biosynthesis of three pancreatic enzymes. Biochim. Biophys. Acta 498: 76–82, 1977.
 16. Desnuelle, P., J. P. Reboud, and A. Ben Abdeljlil. Influence of the composition of the diet on the enzyme content of rat pancreas. In: The Exocrine Pancreas, edited by A. V. S. de Reuck and M. P. Cameron. Boston, MA: Little, Brown, 1962, p. 90–114. (Ciba Found. Symp.).
 17. Dynan, W. S., and R. Tjian. The promoter‐specific transcription factor SpI binds to upstream sequences in the SV40 early promoter. Cell 35: 79–87, 1983.
 18. Efstratiadis, A., J. W. Posakony, T. Maniatis, R. M. Lawn, C. O'Connell, R. A. Spritz, J. K. DeRiel, B. G. Forget, S. M. Weissman, J. L. Slightom, A. E. Blechl, O. Smithies, F. E. Baralle, C. C. Shoulders, and N. J. Proudfoot. The structure and evolution of the human beta‐globin gene family. Cell 21: 653–668, 1980.
 19. Faichney, A., W. Y. Chey, Y. C. Kim, K. Y. Lee, and M. S. Kim. Effect of sodium oleate on plasma secretin concentration and pancreatic secretion in dog. Gastroenterology 81: 458–462, 1981.
 20. Gillies, S. D., S. L. Morrison, V. T. Oi, and S. Tonegawa. A tissue‐specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33: 717–728, 1983.
 21. Giorgi, D., J. P. Bernard, R. Lapointe, and J. C. Dagorn. Regulation of amylase messenger RNA concentration in rat pancreas by total food content. EMBO J. 3: 1521–1524, 1984.
 22. Giorgi, D., W. Renaud, J. P. Bernard, and J. C. Dagorn. Regulation of proteolytic enzyme activities and mRNA concentrations in rat pancreas by food content. Biochem. Biophys. Res. Commun. 127: 937–942, 1985.
 23. Goodbourn, S., H. Burnstein, and T. Maniatis. The β‐interferon gene enhancer is under negative control. Cell 45: 601–610, 1986.
 24. Grifo, J. A., S. M. Tahara, J. P. Leis, M. A. Morgan, A. J. Shatkin, and W. C. Merrick. Characterization of eukaryotic initiation factor 4A, a protein involved in ATP‐dependent binding of globin mRNA. J. Biol. Chem. 257: 5246–5252, 1982.
 25. Grifo, J. A., S. M. Tahara, M. A. Morgan, A. J. Shatkin, and W. C. Merrick. New initiation factor activity eIF4F required for globin mRNA translation. J. Biol. Chem. 258: 5804–5810, 1983.
 26. Grossman, A., A. M. Boctor, P. Band, and B. Lane. Role of steroids in secretions—modulating effect of triamcinolone and estradiol on protein synthesis and secretion from the rat exocrine pancreas. J. Steroid Biochem. 19: 1069–1081, 1983.
 27. Grossman, M. I., H. Greengard, and A. C. Ivy. The effect of dietary composition of pancreatic enzymes. Am. J. Physiol. 138: 676–682, 1943.
 28. Hagenbüchle, O., U. Schibler, S. Petrucco, G. C. Van Tuyle, and P. K. Wellauer. Expression of mouse Amy‐2a alpha‐amylase genes is regulated by strong pancreas‐specific promoters. J. Mol. Biol. 185: 285–293, 1985.
 29. Han, J. H., L. Rall, and W. J. Rutter. Selective expression of rat pancreatic genes during embryonic development. Proc. Natl. Acad. Sci. USA 83: 110–114, 1986.
 30. Huez, G., C. Bruck, and Y. Cleuter. Translational stability of native and deadenylated rabbit globin mRNA injected into HeLa cells. Proc. Natl. Acad. Sci. USA 78: 908–911, 1981.
 31. Korc, M., D. Owerbach, C. Quinto, and W. J. Rutter. Pancreatic islet‐acinar cell interaction: amylase messenger RNA levels are determined by insulin. Science Wash. DC 213: 351–353, 1981.
 32. Kozak, M. Comparison of initiation of protein synthesis in prokaryotes, eukaryotes and organelles. Microbiol. Rev. 47: 1–45, 1983.
 33. Kozak, M. Point mutations close to the AUG initiation codon affect the efficiency of translation of rat preproinsulin in vivo. Nature Lond. 308: 241–246, 1984.
 34. Kozak, M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 12: 857–872, 1984.
 35. Kozak, M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283–292, 1986.
 36. Liddle, R. A., G. M. Green, C. K. Conrad, and J. A. Williams. Proteins but not amino acids, carbohydates, or fats stimulate cholecystokinin secretion in the rat. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14): G243–G248, 1986.
 37. Logsdon, C. D., J. Moessner, J. A. Williams, and I. D. Goldfine. Glucocorticoids increase amylase mRNA levels, secretory organelles, and secretion in pancreatic acinar AR42J cells. J. Cell Biol. 100: 1200–1208, 1985.
 38. Logsdon, C. D., K. J. Perot, and A. R. McDonald. Mechanism of glucocorticoid‐induced increase in pancreatic amylase gene transcription. J. Biol. Chem. 262: 15765–15769, 1987.
 39. Lütcke, H., K. C. Chow, F. S. Mickel, K. A. Moss, H. F. Kern, and G. A. Scheele. Selection of AUG initiation codons differs in plants and animals. EMBO J. 6: 43–48, 1987.
 40. MacDonald, R. J., M. Crerar, W. Swain, R. Pictet, G. Thomas, and W. Rutter. Structure of a family of rat amylase genes. Nature Lond. 287: 117–122, 1980.
 41. MacDonald, R. J., S. Stary, and G. H. Swift. Two similar but nonallelic rat pancreatic trypsinogens. J. Biol. Chem. 257: 9724–9732, 1982.
 42. McKnight, S., and R. Tjian. Transcriptional selectivity of viral genes in mammalian cells. Cell 36: 795–805, 1986.
 43. Mount, S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 10: 459–472, 1982.
 44. Myers, R. M., K. Tilly, and T. Maniatis. Fine structure genetic analysis of a β‐globin promoter. Science Wash. DC 232: 613–618, 1986.
 45. Nevins, J. R. The pathway of eukaryotic mRNA formation. Annu. Rev. Biochem. 52: 441–466, 1983.
 46. Niebel, W., M. V. Singer, L. E. Hanssen, and H. Goebell. Effect of atropine on pancreatic bicarbonate output and plasma concentrations of immunoreactive secretin in response to intraduodenal stimulants. Scand. J. Gastroenterol. 18: 803–808, 1983.
 47. Ochoa, S. Regulation of protein synthesis initiation in eukaryotes. Arch. Biochem. Biophys. 223: 325–349, 1983.
 48. Ohlsson, B. Characterization and Physiological Function of Proteinases of Pancreatic Origin and Proteinase Inhibitors in the Developing Pig. Univ. of Lund, Sweden, 1987. Thesis.
 49. Palla, J., A. Ben Abdeljlil, and P. Desnuelle. Action de l'insuline sur le biosynthese se l'amylase et de quelques autres enzymes du pancreas de rat. Biochim. Biophys. Acta 158: 25–35, 1968.
 50. Pavlov, I. P. The Digestive Glands. Birmingham, AL: Classics Med. Library, 1897, p. 41–42.
 51. Pelham, H. R. B., and M. Bienz. A synthetic heat shock promoter element confers heat inducibility on the herpes simplex virus thymidine kinase gene. EMBO J. 1: 1473–1477, 1982.
 52. Pictet, R., and W. J. Rutter. Development of the embryonic endocrine pancreas. In: Handbook of Physiology. Endocrinology. Endocrine Pancreas, edited by D. F. Steiner and N. Freinkel. Washington, DC: Am. Physiol. Soc., 1972, sect. 7, vol. I, chapt. 2, p. 25–66.
 53. Pinsky, S., S. LaForge, and G. Scheele. Differential regulation of trypsinogen mRNA translation: full‐length mRNA sequences encoding two oppositely charged trypsinogen isoenzymes in the dog pancreas. Mol. Cell. Biol. 5: 2669–2676, 1985.
 54. Pittet, A.‐C., and U. Schibler. Mouse α‐amylase loci, Amy‐1a and Amy‐2a, are closely linked. J. Mol. Biol. 182: 359–365, 1985.
 55. Rall, L., R. Pictet, S. Githens, and W. J. Rutter. Glucocorticoids modulate the in vitro development of the embryonic rat pancreas. J. Cell Biol. 75: 398–409, 1977.
 56. Rausch, U., P. Vasiloudes, K. Rüdiger, and H. F. Kern. In‐vivo stimulation of rat pancreatic acinar cells by infusion of secretin. II. Changes in individual rates of enzyme and isoenzyme biosynthesis. Cell Tissue Res. 242: 641–644, 1985.
 57. Rausch, U., P. Vasiloudes, K. Rüdiger, H. Kern, and G. Scheele. Synthesis of lipase in the rat pancreas is regulated by secretin. Pancreas 1: 522–528, 1986.
 58. Reed, R., and T. Maniatis. A role for exon sequences and splice‐site proximity in splice‐site selection. Cell 46: 681–690, 1986.
 59. Reinberg, D., M. Horikoshi, and R. G. Roeder. Factors involved in specific transcription in mammalian RNA polymerase II. Functional analysis of initiation factors IIA and IID and identification of a new factor operating at sequences downstream of the initiation site. J. Biol. Chem. 262: 3322–3330, 1987.
 60. Renaud, W., D. Giorgi, J. Jovanna, and J. C. Dagorn. Regulation of concentrations of mRNA for amylase, trypsinogen I and chymotrypsinogen B in rat pancreas by secretagogues. Biochem. J. 235: 305–308, 1986.
 61. Renkawitz, R., G. Schütz, D. von der Ahe, and M. Beato. Sequences in the promoter region of the chicken lysosome gene required for steroid regulation and receptor binding. Cell 37: 503–510, 1984.
 62. Richards, R. I., A. Heguy, and M. Karin. Structural and functional analysis of the human metallothionein‐IA gene: differential induction by metal ions and glucocorticoids. Cell 37: 263–272, 1984.
 63. Saab, J. E., P. Godfrey, and P. M. Brannon. Adaptive response of rat pancreatic lipase to dietary fat: effects of amount and type of fat. J. Nutr. 116: 892–899, 1986.
 64. Schaffalitsky de Muckadell, O. B., O. Olsen, P. Cantor, and E. Magid. Concentrations of secretin and CCK in plasma and pancreaticobiliary secretion in response to intraduodenal acid and fat. Pancreas 1: 536–543, 1986.
 65. Scheele, G. A. Two‐dimensional gel analysis of soluble proteins. Characterization of guinea pig exocrine pancreatic proteins. J. Biol. Chem. 250: 5375–5385, 1975.
 66. Scheele, G. A. Analysis of the secretory process in the exocrine pancreas by two‐dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Methods Cell Biol. 23: 345–358, 1981.
 67. Scheele, G. A. Regulation of gene expression in the exocrine pancreas. In: The Exocrine Pancreas: Biology, Pathobiology, and Diseases, edited by V. L. W. Go, F. P. Brooks, E. P. DiMagno, J. D. Gardner, E. Lebenthal, E. P. DiMagno, and G. A. Scheele. New York: Raven, 1986, p. 55–67.
 68. Scheele, G. A. Two dimensional electrophoresis in the analysis of exocrine pancreatic proteins. In: The Exocrine Pancreas: Biology, Pathobiology, and Diseases, edited by V. L. W. Go, F. P. Brooks, E. P. DiMagno, J. D. Gardner, E. Lebenthal, and G. A. Scheele. New York: Raven, 1986, p. 185–192.
 69. Scheidereit, C., and M. Beato. Contacts between hormone receptor and DNA double helix within a glucocorticoid regulatory element of mouse mammary tumor virus. Proc. Natl. Acad. Sci. USA 81: 3029–3033, 1984.
 70. Schibler, U., O. Hagenbüchle, P. K. Wellauer, and A. C. Pittet. Two promoters of different strengths control the transcription of the mouse alpha‐amylase gene Amy‐1a in the parotid gland and the liver. Cell 33: 501–508, 1983.
 71. Schibler, U., A. C. Pittet, R. Young, O. Hagenbüchle, M. Tosi, S. Gellman, and P. Wellauer. The mouse alpha‐amylase multigene family: sequence organization of members expressed in the pancreas, salivary gland and liver. J. Mol. Biol. 155: 247–266, 1982.
 72. Schick, J., H. Kern, and G. Scheele. Hormonal stimulation in the exocrine pancreas results in coordinate and anticoordinate regulation of protein synthesis. J. Cell Biol. 99: 1559–1564, 1984.
 73. Schick, J., R. Verspohl, H. Kern, and G. Scheele. Two distinct adaptive responses in the synthesis of exocrine pancreatic enzymes to inverse changes in protein and carbohydrate in the diet. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G611–G616, 1984.
 74. Searle, P. F., G. W. Stuart, and R. D. Palmiter. Building a metal‐responsive promoter with synthetic regulatory elements. Mol. Cell. Biol. 5: 1480–1489, 1985.
 75. Shatkin, A. J. Cap structure at the 5' end of eukaryotic cellular and viral mRNAs. Cell 9: 645–652, 1976.
 76. Slater, E. P., O. Rabenau, M. Karin, J. D. Baxter, and M. Beato. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol. Cell. Biol. 5: 2984–2992, 1985.
 77. Snook, J. T. Dietary regulation of pancreatic enzymes in the rat with emphasis on carbohydrate. Am. J. Physiol. 221: 1383–1387, 1971.
 78. Söling, H. D., and K. O. Uunger. The role of insulin in the regulation of alpha‐amylase synthesis in the rat pancreas. Eur. J. Clin. Invest. 2: 199–212, 1972.
 79. Stratowa, C., and W. J. Rutter. Selective regulation of trypsin gene expression by calcium and by glucose starvation in a rat exocrine pancreas cell line. Proc. Natl. Acad. Sci. USA 83: 4292–4296, 1986.
 80. Stuart, G. W., P. F. Searle, and R. D. Palmiter. Identification of multiple metal regulatory elements in mouse metal‐lothionein‐I promoter by assaying synthetic sequences. Nature Lond. 317: 828–831, 1985.
 81. Suske, G., M. Wenz, A. C. Cato, and M. Beato. The uteroglobin gene region: hormonal regulation, repetitive elements and complete nucleotide sequence of the gene. Nucleic Acids Res. 11: 2257–2271, 1983.
 82. Swift, G., C. Craik, S. Stary, C. Quinto, R. Lahaie, W. Rutter, and R. MacDonald. Structure of the two related elastase genes expressed in the rat pancreas. J. Biol. Chem. 259: 14271–14278, 1984.
 83. Swift, G. H., R. E. Hammer, R. J. MacDonald, and R. L. Brinster. Tissue specific expression of rat pancreatic elastase I gene in transgenic mice. Cell 38: 639–646, 1984.
 84. Tahara, S. M., M. A. Morgan, and A. J. Shatkin. Two forms of purified 7mG‐cap binding protein with different effects on capped mRNA translation in extracts of uninfected and polio‐virus‐infected HeLa cells. J. Biol. Chem. 256: 7691–7694, 1981.
 85. Treisman, R. Transient accumulation of c‐fos RNA following serum stimulation requires a conserved 5' element and c‐fos 3' sequences. Cell 42: 889–902, 1985.
 86. Trimble, E. R., R. Bruzzone, and D. Belin. Insulin resistance is accompanied by impairment of amylase gene expression in the exocrine pancreas of the obese Zucker rat. Biochem. J. 237: 807–812, 1986.
 87. Trimble, E. R., U. Rausch, and H. F. Kern. Changes in individual rates of pancreatic enzyme and isoenzyme biosynthesis in the obese Zucker rat. Biochem. J. 248: 771–777, 1987.
 88. Van Knippenberg, P. H., J. M. A. Van Kimmenade, and H. A. Heus. Phylogeny of the conserved 3' terminal structure of the RNA of small ribosomal subunits. Nucleic Acids Res. 12: 2595–2604, 1984.
 89. von der Ahe, D., S. Janich, C. Scheidereit, R. Renkawitz, G. Schütz, and M. Beato. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. Nature Lond. 313: 706–709, 1985.
 90. Walker, M., T. Edlund, A. Boulet, and W. Rutter. Cell specific expression controlled by the 5' flanking region of insulin and chymotrypsin genes. Nature Lond. 306: 557–561, 1983.
 91. Weiher, H., M. König, and P. Gruss. Multiple point mutations affecting the simian virus 40 enhancer. Science Wash. DC 219: 626–631, 1983.
 92. Welch, J. W., J. I. Garrels, G. P. Thomas, J. J.‐C. Lin, and J. R. Feramisco. Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose‐ and calcium‐ionophore regulated proteins. J. Biol. Chem. 258: 7102–7111, 1983.
 93. Wicker, C., and A. Puigserver. Effects of inverse changes in dietary lipid and carbohydrate on the synthesis of some pancreatic secretory proteins. Eur. J. Biochem. 162: 25–30, 1987.
 94. Wicker, C., A. Puigserver, and G. A. Scheele. Dietary regulation of levels of active mRNA coding for amylase and serine protease zymogens in the rat pancreas. Eur. J. Biochem. 139: 381–387, 1984.
 95. Young, R. A., O. Hagenbüchle, and U. Schibler. A single mouse alpha‐amylase gene specifies two different tissue‐specific mRNAs. Cell 23: 451–458, 1981.
 96. Zinn, K., D. DiMaio, and J. DeMaeyer‐Guignard. Identification of two distinct regulatory regions adjacent to the human beta‐interferon gene. Cell 34: 865–879, 1983.
 97. Zinn, K., and T. Maniatis. Detection of factors that interact with the human beta‐interferon regulatory region in vivo by DNase I footprinting. Cell 45: 611–618, 1986.

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Article Title: Selective Regulation of Gene Expression in the Exocrine Pancreas
 

How to Cite

George A. Scheele, Horst F. Kern. Selective Regulation of Gene Expression in the Exocrine Pancreas. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 499-513. First published in print 1989. doi: 10.1002/cphy.cp060325