This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Delhanty, P. J. D. Articles by Baxter, R. C. Search for Related Content PubMed PubMed Citation Articles by Delhanty, P. J. D. Articles by Baxter, R. C.

The Regulation of Acid-Labile Subunit Gene Expression and Secretion by Cyclic Adenosine 3',5'-Monophosphate¹

Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia

Address all correspondence and requests for reprints to: Dr. Patric J. D. Delhanty, Kolling Institute of Medical Research, St. Leonards, New South Wales 2065, Australia. E-mail: delhanty{at}med.usyd.edu.au

Circulating acid-labile subunit (ALS) is mainly hepatocyte derived and is GH dependent. ALS buffers the metabolic effects of the insulin-like growth factors by sequestering them in a ternary complex with insulin-like growth factor-binding protein-3. Nutritional regulation of ALS may be mediated by cAMP and changes in circulating GH levels or tissue GH sensitivity. Therefore, we examined the regulation by cAMP of ALS steady state messenger RNA (mRNA) levels and secretion in isolated hepatocytes under basal and GH-induced conditions. Increasing intracellular cAMP in primary hepatocytes produced a dose-dependent suppression of ALS mRNA levels and secretion. This effect was not related to a reduction in mRNA stability. In the presence of GH there was a parallel suppression of mRNA levels and secretion. However, under basal conditions cAMP had less effect on ALS mRNA levels than on secretion. Thus, in the absence of GH, expression of ALS may be predominantly posttranscriptionally regulated by cAMP. Our study suggests that cAMP affects ALS gene transcription, perhaps by interrupting the GH signaling pathway, and also inhibits posttranscriptional events in ALS expression.

This article has been cited by other articles:

				A. J. Butt, K. A. Dickson, F. McDougall, and R. C. Baxter Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo J. Biol. Chem., August 8, 2003; 278(32): 29676 - 29685. [Abstract] [Full Text] [PDF]

				S.-E. Kong, R. C. Baxter, and P. J. D. Delhanty Age-Dependent Regulation of the Acid-Labile Subunit in Response to Fasting-Refeeding in Rats Endocrinology, December 1, 2002; 143(12): 4505 - 4512. [Abstract] [Full Text] [PDF]

				F. de Groof, K. F. M. Joosten, J. A. M. J. L. Janssen, E. D. de Kleijn, J. A. Hazelzet, W. C. J. Hop, P. Uitterlinden, J. van Doorn, and A. C. S. Hokken-Koelega Acute Stress Response in Children with Meningococcal Sepsis: Important Differences in the Growth Hormone/Insulin-Like Growth Factor I Axis between Nonsurvivors and Survivors J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3118 - 3124. [Abstract] [Full Text] [PDF]

				P. J. D. Delhanty, C. D. Scott, S. Babu, and R. C. Baxter Acid-labile subunit regulation during the early stages of liver regeneration: implications for glucoregulation Am J Physiol Endocrinol Metab, February 1, 2001; 280(2): E287 - E295. [Abstract] [Full Text] [PDF]

				R. P. Rhoads, P. L. Greenwood, A. W. Bell, and Y. R. Boisclair Organization and Regulation of the Gene Encoding the Sheep Acid-Labile Subunit of the 150-Kilodalton Insulin-Like Growth Factor-Binding Protein Complex Endocrinology, April 1, 2000; 141(4): 1425 - 1433. [Abstract] [Full Text] [PDF]

				G. Van den Berghe, R. C. Baxter, F. Weekers, P. Wouters, C. Y. Bowers, and J. D. Veldhuis A Paradoxical Gender Dissociation within the Growth Hormone/Insulin-Like Growth Factor I Axis during Protracted Critical Illness J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 183 - 192. [Abstract] [Full Text]

				J. Frystyk, P. J. D. Delhanty, C. Skjarbak, and R. C. Baxter Changes in the circulating IGF system during short-term fasting and refeeding in rats Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E245 - E252. [Abstract] [Full Text] [PDF]

				A. J. Butt, S. M. Firth, M. A. King, and R. C. Baxter Insulin-like Growth Factor-binding Protein-3 Modulates Expression of Bax and Bcl-2 and Potentiates p53-independent Radiation-induced Apoptosis in Human Breast Cancer Cells J. Biol. Chem., December 8, 2000; 275(50): 39174 - 39181. [Abstract] [Full Text] [PDF]