Upregulation of hepatic prolactin receptor gene expression by 17β-estradiol following trauma-hemorrhage

Although studies show protective effects of 17β-estradiol (E ₂) or prolactin (PRL) treatment in male rats after trauma-hemorrhage (T-H), the mechanism of the salutary effects of these agents remains unknown. Because E₂ modulates PRL receptor (PRL-R) expression in the liver, we examined whether E₂ treatment after T-H has any effects on hepatic PLR-R gene expression. Male Sprague-Dawley rats were subjected to trauma (i.e., 5-cm midline laparotomy) and hemorrhage (35-40 mmHg for 90 min) followed by fluid resuscitation (Ringer lactate) or sham operation and then treated with E₂ (50 μg/kg body wt sc) or vehicle immediately before resuscitation. Liver samples were collected at 3 h thereafter, and PRL-R mRNA expression was determined by PCR. Liver expression of PRL-R short-form gene was unaffected by T-H, whereas that of the long-form gene was suppressed. Treatment of T-H rats with E₂ significantly increased PRL-R short-form gene expression and normalized PRL-R long-form gene expression to sham levels. In the isolated hepatocytes, PRL-R short-form gene expression was predominant compared with the long-form gene. In contrast, only the short form was detected in Kupffer cells. In vitro treatment by E₂ demonstrated an increase in the PRL-R long-form gene in hepatocytes, but E₂ had no effect on PRL-R short-form gene expression in either the Kupffer cells or hepatocytes. Thus E₂ treatment after T-H in males appears to directly upregulate PRL-R long-form gene expression in hepatocytes. However, the upregulation of the PRL-R short form might involve the interaction of multiple cell types in the liver.