Endocrine Abstracts

PRL has long been recognized as a hormone that regulates both cell proliferation and differentiation in the mammary gland. Current theory proposes that it is the coexisting steroidal environment which dictates whether PRL is mainly proliferative, as it is during pregnancy, or mainly differentiative, as it is during lactation. While major changes in the steroidal environment may contribute to a shift in response by the mammary gland, other tissues which show both responses to PRL have a fairly constant steroidal environment. Thus, we have hypothesized that the form of PRL to which the tissue is exposed is also relevant. To test this hypothesis, we have administered physiological quantities of recombinant unmodified PRL (U-PRL) and a molecular mimic of phosphorylated PRL (S179D PRL) to male and female rats in different physiological states and have assessed the effect on the morphology of target tissues, tissue specific gene expression and blood levels of relevant steroid hormones. In the mammary gland and prostate, U-PRL produced proliferative changes while decreasing tissue-specific gene expression. S179D PRL, by contrast, inhibited proliferation while promoting a more differentiated morphology and increasing tissue-specific gene expression. Effects on the mammary gland were independent of progesterone, estradiol and corticosterone and those in the prostate were independent of testosterone and dihydrotestosterone. We conclude from these and other in vivo and in vitro studies that U-PRL is the form that promotes proliferation while phosphorylated PRL antagonizes this effect and promotes differentiation. We propose that both forms need to be in balance for proper tissue health, with the ratio of one to the other dictating the type of PRL effect.
These animal studies were performed in accordance with National Institutes of Health guidelines and were supported by NIH grant DK61005 and the Army Breast Cancer Research Program, DAMD 17-00-1-0180.