Expression of growth hormone receptor and its mRNA in hepatic cirrhosis

AIM: To investigate the expression of growth hormone receptor (GHR) and mRNA of GHR in cirrhotic livers of rats with the intension to find the basis for application of recombinant human growth hormone (rhGH) to patients with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in SpragueDawley rats by administration of thioacetamide intraperitoneally for 9-12 weeks. Collagenase Ⅳ was perfused in situ for isolation of hepatocytes. The expression of GHR and its mRNA in cirrhotic livers was studied with radio-ligand binding assay, RT-PCR and digital image analysis.RESULTS: One class of specific growth hormone-binding site, GHR, was detected in hepatocytes and hepatic tissue of cirrhotic livers. The binding capacity of GHR (RT, fmol/mg protein) in rat cirrhotic liver tissue (30.8±1.9) was significantly lower than that in normal control (74.9±3.9) at the time point of the ninth week after initiation of induction of cirrhosis (n=10, P＜0.05), and it decreased gradually along with the accumulation of collagen in the process of formation and development of liver cirrhosis (P＜0.05). The number of binding sites (×10 4/cell) of GHR on rat cirrhotic hepatocytes (0.86±0.16) was significantly lower than that (1.28±0.24)in control (n= 10, P＜0.05). The binding affinity of GHR among liver tissue, hepatocytes of various groups had no significant difference (P＞0.05). The expression of GHR mRNA (riOD,pixel) in rat cirrhotic hepatic tissues (23.3±3.1) was also significantly lower than that (29.3±3.4) in normal control (n=10, P＜0.05).CONCLUSION: The growth hormone receptor was expressed in a reduced level in liver tissue of cirrhotic rats,and lesser expression of growth hormone receptors was found in a later stage of cirrhosis. The reduced expression of growth hormone receptor was partly due to its decreased expression on cirrhotic hepatocytes and the reduced expression of its mRNA in cirrhotic liver tissue.

Protective effects of recombinant human growth hormone on cirrhotic rats

AIM: To investigate the effects and molecular mechanismsof recombinant human growth hormone (rhGH) onprotecting liver function and alleviating portal hypertensionof liver cirrhotic rats.METHODS: Liver cirrhosis of male Sprague-Dawley ratswas induced by administration of thioacetamide. The ratswith or without liver cirrhosis were randomly divided intofour groups. Group A consisted of the normal rats wastreated with normal saline (NS), group B consisted of thenormal rats was treated with rhGH, group C consisted ofcirrhotic rats was treated with NS, and group D consistedof cirrhotic rats was treated with rhGH. The rats of differentgroups were subcutaneously injected with 0.5 mL of NS or333 ng/kg of rhGH daily for 7 d. After treatments, thefollowing parameters were examined, including GH-bindingcapacity (RO by 12SI-hGH binding, growth hormone receptormRNA(GHR mRNA) expression by RT-PCR, relative contentof collagen (RCC) by histomorphomertry, and level ofmalon-dialdehyde (MDA) and superoxide dismutase (SOD)in liver tissue by thiobarbituric acid reaction and pyrogallicacid self-oxidation, respectively. Serum albumin (ALB),alanine transaminase (ALT) and portal vein pressure (PVP)were also examined.RESULTS: rhGH up-regulated both the GH-binding capacity(R0 and the expression of GHR mRNA in vivo. RT in groupA (72+12 fmol/mg protein) was significantly higher thanthat in group C (31+4 fmol/mg protein) (P<0.05). RT ingroup B (80+9 fmol/mg protein) increased markedlycompared to group A (P<0.05). RT in group D (40+7 fmol/mgprotein) raised remarkably compared with group C (P<0.05),but less than that in group A, and there was no significantGH binding affinity contrast (Kd) change. The GHR mRNAlevel (iOD, pixel) in group A (29+3) was significantly higherthan that in group C (23+3) (P<0.05). GHR mRNA levelswere significantly raised in group B (56+4) and group D(42+8) compared with groups A and C (29+3 and 23+3,respectively) (P<0.05). Compared with the normal liver,MDA level was higher and SOD level was lower in cirrhoticlivers. After rhGH treatment, MDA level was significantlydeclined to 12.0+2.2 nmol/mg protein and SOD was raisedto 1029+76 U/rag protein in group D (P<0.05). ALB levelsin groups B and D (42+7 g/L and 37+7 g/L, respectively)were significantly raised compared with those in groups Aand C (35+5 g/L and 29+4 g/L, respectively) (P<0.05).ALT level was markedly lower in group D (69+7 U/L)compared to group C (89+15 U/L) (P<0.05), and close togroup A (61+10 U/L). RCC in group C (22.30+3.86%) wassignificantly higher than that in group A (1.14+0.21%) andgroup D (14.70+2.07%) (P<0.05). In addition, rhGHmarkedly alleviated portal hypertension in liver cirrhoticrats (group D vsC, 9.3+1.5 cmH20 vs 14.4+2.0 cmH20)(P<0.05).CONCLUSION: Pharmacological doses of rhGH canincrease RT and GHR mRNA expression, ameliorate liverfunctions, repress fibrosis and decline portal hypertension,suggesting it has potentially clinical usage as a hepatotropicfactor.