Expression of growth hormone receptor and its mRNA in hepatic cirrhosis.
OBJECTIVE
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 Sprague-Dawley 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 (R(T), 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 (X10(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).


CONCLUSIONS
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.
Wang
Hong-Tao
HT
Department of Hepato-biliary Surgery, Sun Yat-Sen Memorial Hospital, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China. sumswht@hotmail.com
Chen
Shuang
S
Wang
Jie
J
Ou
Qing-Jia
QJ
Liu
Chao
C
Zheng
Shu-Sen
SS
Deng
Mei-Hai
MH
Liu
Xiao-Ping
XP
D000081:Acetamides; D000818:Animals; D005786:Gene Expression Regulation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000081:Acetamides; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; C030686:acetamide