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

Objective: In normal subjects, the major form of circulating IGF is th e GH-dependent 150 kDa complex. The liver appears to be the main sourc e of the three components of the 150 kDa complex and, in particular, h epatocytes synthesize the insulin-like growth factor (IGF) peptide and the acid-labile subunit (ALS), whereas Kupffer and sinusoidal endothe lial cells produce IGF-binding protein-3 (IGFBP-3). We have studied th e effects of the somatostatin analog octreotide, TGF-II, des(1-3)IGF-I , transforming growth factor (TGF)-beta 1 and tri-iodothyronine (T3) o n ALS secretion into the medium conditioned by rat hepatocytes in prim ary culture. Methods: The regulation of ALS release was evaluated in t he conditioned medium of adult rat hepatocytes exposed to increasing c oncentrations of test substances or to vehicle alone (control), after gel filtration in basic conditions, by immunoblot using an antiserum g enerated against the N-terminal 34 amino acids of human ALS. Results: The results demonstrate that: 1) octreotide in vitro produces a dose-d ependent inhibition of both basal and GH-stimulated ALS secretion into the hepatocyte conditioned medium; 2) the release of ALS by adult fat 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 v ery 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 pep tides, the IGFBPs, of both, on adult rat hepatocytes in primary cultur e revealed no powerful stimulator, but instead a potent inhibitor of A LS release/synthesis. Our data suggest that the effect of somatostatin on the 150 kDa complex is mediated not only by the reduction in GH co ncentration, but also by a direct inhibition of ALS release or synthes is.