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 |
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Zusammenfassung: | 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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ISSN: | 0193-1849 0002-9513 1522-1555 |
DOI: | 10.1152/ajpendo.1995.268.1.e6 |