Effect on the canine Eck fistula liver of intraportal TGF-β alone or with hepatic growth factors

Abstract

Transforming growth factor-p canceled the hepatocyte proliferation caused. by transforming growth factor-Of when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast. transforming growth factor-p had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected., but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-a and transforming growth factor-p in the modulation of liver growth control. (HEPATOLOGY • q92; 16: 1267-1270 The Eck fistula (portacaval shunt) in dogs is a useful tool in the identification and study of hepatic growthmodulating substances, of which some of the most potent have little or no effect on hepatocytes in culture (1). This operation is followed by tripling of hepatocyte proliferation, atrophy of hepatocytes within 4 days to about half their original volume and establishment of a new stable state after 4 days (2). Growth stimulating substances, when infused into the tied-off central portal vein after this operation, augment further the heightened proliferation of the Eck fistula liver and prevent liver atrophy after creation ofthe fistula (1, 3-7). These effects have been termed hepatotrophic. In contrast, transforming growth factor-(3 (TGF-(3), a known inhibitor of hepatocyte proliferation in vitro (8,9), has the opposite effect in that it suppresses hepatocyte proliferation after creation of the Eck fistula and further reduces the size of the atrophied hepatocytes (1). The striking TGF-(3 effect is easily overridden with insulin (1).

Διερεύνηση Του Μηχανισμού Δράσης Της Ηπατικής Διεγερτικής Ουσίας ( HSS) Στην Κίρρωση

“…• Τις ιδοσυγκρασιακές ή µη προβλέψιµες, που προκαλούν τοξικότητα σε µικρό ποσοστό των ανθρώπων (Zimmerman 1990). (Blomquist, 1957, Bucher 1967, 1963, Fisher et al 1971, Morley and Kington, 1973 LaBrecque and Pesch 1975, LaBrecque et al 1979, 1982a, 1982b, 1984, Ove et al 1989, Francavilla et al 1991, 1992, Gupta et al 1992, Mei et al 1993 Francavilla et al 1986Francavilla et al , 1987Francavilla et al , 1991aFrancavilla et al , 1991bFrancavilla et al , 1992Francavilla et al , 1993 et al , 1982aet al , 1982bet al , Yao et al, 1990 al 1979, 1982a, 1982b, 1984, Fleig et al, 1986, Yao et al 1990, 1992, Mei et al 1993, Hwang et al 1995, Kyprianidis et al 1996, 1999 Francavilla et al 1986Francavilla et al , 1987Francavilla et al , 1991aFrancavilla et al , 1991bFrancavilla et al , 1992Francavilla et al , 1993 (Francavilla et al 1987…”