Expression and distribution of the prolactin receptor in normal rat liver and in experimental liver cirrhosis

Recent results have suggested a role for prolactin (PRL) as a regeneration factor in the liver. In order to investigate the involvement of prolactin i n the pathogenesis of liver cirrhosis, we studied the expression of the pro lactin receptor (PRLR) and PRL during the development of cirrhosis in an an imal model. 30 male rats were exposed to CCl4 by inhalation. Phenobarbitone was added to the drinking water to accelerate the formation of toxic metab olites by enzyme induction. Two control groups of 30 animals each were trea ted with phenobarbitone only or received no treatment. 10 animals of each g roup were sacrificed 35, 55, and 70 days after initiation of treatment. Liv er tissue was subjected to histological examination, which demonstrated fib rosis of different grades and cirrhosis in the CCl4-treated rats. Expressio n of PRLR mRNA was investigated by mRNA extraction, RT-PCR and computer-sup ported densitometric evaluation. Compared to control liver, PRLR mRNA was e xpressed at a higher level in fibrotic and cirrhotic liver specimens. In no rmal tissue, immunohistochemical staining showed a high concentration of PR LR around the central vein and in the epithelium of the bile ducts. This pa ttern of distribution was lost in fibrosis and cirrhosis. An accumulation o f PRLR was demonstrated within the damaged cells. Neither PRL nor PRL mRNA was detectable in normal, fibrotic, or cirrhotic liver. We conclude that PR LR is distributed in normal rat liver in a typical pattern which is lost wi th increasing fibrosis. PRL is not produced by rat liver, indicating that P RL does not act through autocrine or paracrine mechanisms.