Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy

Abstract

GH accelerates hepatic regeneration in the rat. Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, is considered to be a major regulator of hepatic regeneration. In the present study, the effects of GH and insulin-like growth factor-I (IGF-I) on HGF gene expression in regenerating rat liver was investigated. In hypophysectomized rats treated with GH, hepatic HGF mRNA levels were increased 3 h after partial hepatectomy and reached peak levels after 5 h. In rats with intact pituitaries and in hypophysectomized rats not given GH treatment, HGF mRNA levels in liver were unchanged during the first 5 h following hepatectomy and reached peak levels after 10-18 h. DNA synthesis in the liver of GH-treated rats increased from low levels 10 h after hepatectomy to peak levels after 18 h. In rats without GH treatment the synthesis of DNA was still low 18 h after hepatectomy and was increased after 26 h. Treatment of hypophysectomized rats with IGF-I promoted increases in hepatic HGF mRNA levels and DNA synthesis 3.5 h and 15 h after hepatectomy respectively. HGF mRNA levels were constantly lower after sham-hepatectomy than after partial hepatectomy. In summary, in hypophysectomized rats the responses of hepatic HGF gene expression and DNA synthesis to partial hepatectomy were both accelerated by treatment with GH or IGF-I.

Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver [Review]

“…Intriguingly, GHRLD mice showed insulin resistance, glucose intolerance, increased free fatty acids, decreased triglyceride efflux, and severe steatosis, indicating the physiological importance of GH signaling in the liver. Liver regeneration was impaired in this model and several GH-deficient animal models, indicating that GH also regulates the proliferation capacity of hepatocyte [34][35][36]. Regarding the downstream signaling of the GH receptor, liver-specific JAK2-deficient mice (JAK2L) develop hepatic steatosis [37].…”

Gene Expression Profiling to Identify Oncogenic Determinants of Autocrine Human Growth Hormone in Human Mammary Carcinoma

“…Some of these GH-regulated genes code for trophic factors such as insulin-like growth factor-1 (47), which act in an intermediary role to execute the cellular effects of GH. Indeed, GH has been demonstrated to regulate the level of a number of trophic factors in specific tissues including hepatocyte growth factor in liver (48), epidermal growth factor in kidney (49), basic fibroblast growth factor in chondrocytes (50), interleukin-6 in osteoblasts (51), bone morphogenetic proteins 2 and 4 in fibroblasts (52), interleukin-1␣ and interleukin-1␤ in thymus (53), and preadipocyte factor-1 in adipocytes (54) and islet ␤-cells (55). It is apparent that many of the effects of autocrine hGH on mammary carcinoma cell function are also mediated by genetic regulation of specific trophic factors.…”

Hormônio de crescimento na regeneração hepática em ratos

“…7 Moolten et al e Ekberg et al demonstraram que a administração de hormônio de crescimento (GH) ou de fator de crescimento semelhante à insulina (IGF-I) aceleram a síntese de DNA, e Baruch et al concluíram que na regeneração hepática a taxa de hormônio de crescimento ligado à proteína está aumentada. 3,6,9 Asakawa et al verificaram que a injeção deste hormônio não só acelera a regeneração após as ressecções como auxilia na recuperação das disfunções hepáticas em ratos. 5 Sakamoto et al observaram que, em ratos adrenalectomizados, a oferta de hormônio de crescimento produz elevação da taxa de precursores do DNA nos hepatócitos em regeneração.…”

“…1 Hepatócitos podem ser induzidos a sintetizar DNA e a se duplicar após hepatectomias parciais ou adminis-do a importância do hormônio de crescimento. 3 5,6 O presente trabalho tem por objetivo conhecer a influência do hormônio de crescimento sobre a regeneração hepática em ratos.…”