Opposite effects of unmodified prolactin and a molecular mimic of phosphorylated prolactin on morphology and the expression of prostate specific genes in the normal rat prostate

BACKGROUND. In the current study, we have investigated the individual roles of unmodified, wild-type prolactin (WT PRL) and a molecular mimic of phosphorylated prolactin (S179D PRL) in the normal rat prostate. METHODS. In the first animal experiment, recombinant WT PRL and S179D PRL were delivered to adult male rats at a rate of 14 μg/kg per day for 3 weeks. In the second animal experiment, two subcutaneous (200 μg/kg) injections of long-acting forms of the two PRLs were given to adult male rats on day 1 and day 22 for a total of 5.5 weeks of treatment. RESULTS. The different forms of PRL had opposite effects on the normal rat prostate, independently of androgens. WT PRL promoted morphologic changes in prostate epithelium consistent with preparation for cell proliferation, whereas S179D PRL produced morphologic evidence of a more differentiated epithelium. Northern blot analysis of expression of the two major prostate specific proteins, prostatein and probasin, showed that WT PRL decreased, whereas S179D PRL increased, the expression of the mRNAs for these two proteins. At the same time, S179D PRL reduced both testosterone and dihydrotestosterone levels. CONCLUSION. We conclude that PRL is an important modulator of normal rat prostate biology and that different forms of PRL have specific functions. The molecular mimic of phosphorylated PRL, S179D PRL, is the most important in terms of epithelial cell differentiation.