Effect of the somatostatin analog, octreotide, and of other hormones on the release of the acid-labile subunit of the 150 kDa complex by rat hepatocyte in primary culture

Department of Endocrinology and Metabolism, University of Genova, Italy.

OBJECTIVE: In normal subjects, the major form of circulating IGF is the GH-dependent 150 kDa complex. The liver appears to be the main source of the three components of the 150 kDa complex and, in particular, hepatocytes synthesize the insulin-like growth factor (IGF) peptide and the acid-labile subunit (ALS), whereas Kupffer and sinusoidal endothelial cells produce IGF-binding protein-3 (IGFBG-3). We have studied the effects of the somatostatin analog octreotide, IGF-II des(1-3)IGF-I, transforming growth factor (TGF)-beta 1 and tri-iodothyronine (T3) on ALS secretion into the medium conditioned by rat hepatocytes in primary culture. METHODS: The regulation of ALS release was evaluated in the conditioned medium of adult rat hepatocytes exposed to increasing concentrations of test substances or to vehicle alone (control), after gel filtration in basic conditions, by immunoblot using an antiserum generated against the N-terminal 34 amino acids of human ALS. RESULTS: The results demonstrate that: 1) octreotide in vitro produces a dose-dependent inhibition of both basal and GH-stimulated ALS secretion into the hepatocyte conditioned medium; 2) the release of ALS by adult rat hepatocytes is not affected by the presence during the incubation of des(1-3)IGF-I or IGF-II; 3) an inhibitory effect, although only with very high doses, can be observed after treatment with TGF-beta 1; and 4) a small but significant increase of ALS released into the medium can be seen when hepatocytes are treated with T3. CONCLUSIONS: Evaluation of the effect of substances known to affect the production of IGF peptides, the IGFBPs, or both, on adult rat hepatocytes in primary culture revealed no powerful stimulator, but instead a potent inhibitor of ALS release/synthesis. Our data suggest that the effect of somatostatin on the 150 kDa complex is mediated not only by the reduction in GH concentration, but also by a direct inhibition of ALS release or synthesis.

This article has been cited by other articles:

				K. Pistevou-Gombaki, N. Eleftheriadis, G. A Plataniotis, I. Sofroniadis, and V. E Kouloulias Octreotide for palliative treatment of hepatic metastases from non-neuroendocrine primary tumours: evaluation of quality of life using the EORTC QLQ-C30 questionnaire Palliative Medicine, April 1, 2003; 17(3): 257 - 262. [Abstract] [PDF]

				M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, and A. Barreca Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3 J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1091 - 1098. [Abstract] [Full Text]

				A. Juul, S. Møller, E. Mosfeldt-Laursen, M. H. Rasmussen, T. Scheike, S. A. Pedersen, K. W. Kastrup, H. Yu, J. Mistry, S. Rasmussen, et al. The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor Binding Protein Complex in Serum: Hepatosplanchnic Release, Diurnal Variation, Circulating Concentrations in Healthy Subjects, and Diagnostic Use in Patients with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4408 - 4415. [Abstract] [Full Text]