Hormonal regulation of albumin gene expression in primary cultures of rat hepatocytes

S. R. Kimball, R. L. Horetsky and L. S. Jefferson Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033. When primary cultures of rat hepatocytes were placed in a chemically defined serum-free medium containing a combination of insulin, gl...

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Veröffentlicht in:American journal of physiology: endocrinology and metabolism 1995-01, Vol.268 (1), p.E6-E14
Hauptverfasser: Kimball, S. R, Horetsky, R. L, Jefferson, L. S
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creator Kimball, S. R
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Jefferson, L. S
description S. R. Kimball, R. L. Horetsky and L. S. Jefferson Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033. When primary cultures of rat hepatocytes were placed in a chemically defined serum-free medium containing a combination of insulin, glucagon, and dexamethasone, the synthesis of albumin and total protein and the cellular content of RNA and DNA were maintained at constant values for 8 days. Despite the constant rate of albumin synthesis, secretion of the protein increased more than twofold during the initial 4 days in culture and was then maintained at a value similar to that observed in vivo through day 8. This observation suggested an initial defect in albumin secretion that was corrected with time in culture. Deprivation of insulin between days 2 and 5 resulted in a decline in albumin secretion to approximately 40% of the control value. The decline in albumin secretion was accompanied by proportional decreases in albumin synthesis, albumin mRNA, and albumin gene transcription. Return of insulin-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8. Deprivation of either glucagon or dexamethasone also resulted in reduced albumin synthesis and secretion accompanied by proportional decreases in albumin mRNA and gene transcription. However, the magnitude of the changes in these parameters was less with glucagon or dexamethasone deprivation compared with insulin deprivation. Return of glucagon- or dexamethasone-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8.
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Deprivation of insulin between days 2 and 5 resulted in a decline in albumin secretion to approximately 40% of the control value. The decline in albumin secretion was accompanied by proportional decreases in albumin synthesis, albumin mRNA, and albumin gene transcription. Return of insulin-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8. Deprivation of either glucagon or dexamethasone also resulted in reduced albumin synthesis and secretion accompanied by proportional decreases in albumin mRNA and gene transcription. However, the magnitude of the changes in these parameters was less with glucagon or dexamethasone deprivation compared with insulin deprivation. 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R</creatorcontrib><creatorcontrib>Horetsky, R. L</creatorcontrib><creatorcontrib>Jefferson, L. S</creatorcontrib><title>Hormonal regulation of albumin gene expression in primary cultures of rat hepatocytes</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol</addtitle><description>S. R. Kimball, R. L. Horetsky and L. S. Jefferson Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033. When primary cultures of rat hepatocytes were placed in a chemically defined serum-free medium containing a combination of insulin, glucagon, and dexamethasone, the synthesis of albumin and total protein and the cellular content of RNA and DNA were maintained at constant values for 8 days. Despite the constant rate of albumin synthesis, secretion of the protein increased more than twofold during the initial 4 days in culture and was then maintained at a value similar to that observed in vivo through day 8. This observation suggested an initial defect in albumin secretion that was corrected with time in culture. Deprivation of insulin between days 2 and 5 resulted in a decline in albumin secretion to approximately 40% of the control value. The decline in albumin secretion was accompanied by proportional decreases in albumin synthesis, albumin mRNA, and albumin gene transcription. Return of insulin-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8. Deprivation of either glucagon or dexamethasone also resulted in reduced albumin synthesis and secretion accompanied by proportional decreases in albumin mRNA and gene transcription. However, the magnitude of the changes in these parameters was less with glucagon or dexamethasone deprivation compared with insulin deprivation. Return of glucagon- or dexamethasone-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8.</description><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Dexamethasone - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>Glucagon - pharmacology</subject><subject>Insulin - pharmacology</subject><subject>Liver - cytology</subject><subject>Liver - physiology</subject><subject>Rats</subject><subject>RNA, Messenger - metabolism</subject><subject>Serum Albumin - biosynthesis</subject><subject>Serum Albumin - genetics</subject><issn>0193-1849</issn><issn>0002-9513</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1PgzAYhRujmXP6E5Zw5Y0BW2gpXJplOpMl3szrpsDLx1IothDl31syspu2Oef0vO2D0JbggBAWvspzD12hA5KmLAjjJCABxDdo7bzQJ4yxW7TGJI18ktD0Hj1Ye8YYc0bDFVrxhGKSRGv0fdCm1Z1UnoFqVHJodOfp0pMqG9um8yrowIO_3oC1s-Wk3jStNJOXj2oYnT7HjRy8Gno56HwawD6iu1IqC0_LvkGn9_1pd_CPXx-fu7ejn1McDz4vMhlRVjAau7WMI44zlvDEHcsijgpK3GtZ7BQKeZhSzDKS5RHnPA9DEkcb9Hyp7Y3-GcEOom1sDkrJDvRoBeck4jTlLsguwdxoaw2UYvmEIFjMNMVCU8w0haMpiNjPA7bLgDFrobjeWvA5_-Xi101V_zYGRF9PjpPS1XStvLb9A6Yvgyk</recordid><startdate>19950101</startdate><enddate>19950101</enddate><creator>Kimball, S. 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S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-7dba345d54645df6370b5878df6fd63d41542568784ec29405b1bc3777c22163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Dexamethasone - pharmacology</topic><topic>Gene Expression - drug effects</topic><topic>Glucagon - pharmacology</topic><topic>Insulin - pharmacology</topic><topic>Liver - cytology</topic><topic>Liver - physiology</topic><topic>Rats</topic><topic>RNA, Messenger - metabolism</topic><topic>Serum Albumin - biosynthesis</topic><topic>Serum Albumin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kimball, S. R</creatorcontrib><creatorcontrib>Horetsky, R. L</creatorcontrib><creatorcontrib>Jefferson, L. 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hormonal regulation of albumin gene expression in primary cultures of rat hepatocytes</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol</addtitle><date>1995-01-01</date><risdate>1995</risdate><volume>268</volume><issue>1</issue><spage>E6</spage><epage>E14</epage><pages>E6-E14</pages><issn>0193-1849</issn><issn>0002-9513</issn><eissn>1522-1555</eissn><abstract>S. R. Kimball, R. L. Horetsky and L. S. Jefferson Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033. When primary cultures of rat hepatocytes were placed in a chemically defined serum-free medium containing a combination of insulin, glucagon, and dexamethasone, the synthesis of albumin and total protein and the cellular content of RNA and DNA were maintained at constant values for 8 days. Despite the constant rate of albumin synthesis, secretion of the protein increased more than twofold during the initial 4 days in culture and was then maintained at a value similar to that observed in vivo through day 8. This observation suggested an initial defect in albumin secretion that was corrected with time in culture. Deprivation of insulin between days 2 and 5 resulted in a decline in albumin secretion to approximately 40% of the control value. The decline in albumin secretion was accompanied by proportional decreases in albumin synthesis, albumin mRNA, and albumin gene transcription. Return of insulin-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8. Deprivation of either glucagon or dexamethasone also resulted in reduced albumin synthesis and secretion accompanied by proportional decreases in albumin mRNA and gene transcription. However, the magnitude of the changes in these parameters was less with glucagon or dexamethasone deprivation compared with insulin deprivation. Return of glucagon- or dexamethasone-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8.</abstract><cop>United States</cop><pmid>7840183</pmid><doi>10.1152/ajpendo.1995.268.1.e6</doi></addata></record>
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subjects Animals
Cells, Cultured
Dexamethasone - pharmacology
Gene Expression - drug effects
Glucagon - pharmacology
Insulin - pharmacology
Liver - cytology
Liver - physiology
Rats
RNA, Messenger - metabolism
Serum Albumin - biosynthesis
Serum Albumin - genetics
title Hormonal regulation of albumin gene expression in primary cultures of rat hepatocytes
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