The role of prolactin in the development of liver cirrhosis

In patients with cirrhosis, prolactin (PRL) is often increased, which can be related to the disturbed metabolism of estrogens. According to recent results, PRL presumably acts as a regeneration factor and is related to growth-associated genes (e.g.: c-myc, c-fos, c-jun) like in the liver. To study the function of PRL in the pathogenesis of cirrhosis, we investigated the prolactin-receptor (PRL-R) and the expression of c-fos and c-jun during the development from healthy to fibrotic and cirrhotic liver in rats under normal and hypoprolactinemic conditions.

4 groups of 15 rats were treated with cabergolin to induce a hypoprolacinemia and with CCl₄ to induce liver dammage and, as controls, with cabergolin or CCl₄ alone or with no treatment. Animals were killed after 35, 50, and 70 days. PRL was messured in serum. RT-PCR were carry out in liver tissue for the expression of PRL, PRL-R, c-fos, and c-jun. Distribution of PRL-R was demonstrated immunhistochemically.

The histological evaluation showed different degrees of fibrosis untill to complete cirrhosis. However, in hypoprolactinemic rats severe grades of liver damage occured later. PRL increased in fibrotic and cirrotic rats, but decreased in cabergolin-treated rats, especially in fibrosis and less in cirrhosis. Refering to controls, expression of RPL-R was increased in cirrhotic livers, though the strongest augmentation was seen in fibrotic tissues. No claer correlation between grades of liver damage and expression of c-fos and c-jun was seen. Immunhistochemically the PRL-R was demonstrated especially around the central veins and in the epithelium of the biliary ducts. This distribution was lost in fibrotis and cirrhotis with an accumulation in the damaged hepatocytes.

Therefore, we assume that PRL takes in a metabolic function in healthy liver and might play a role in the pathogenesis of liver cirrhosis as a regenerative factor wich is not mediated by c-fos or c-jun.