Adrenergic hormones induce extrapituitary prolactin gene expression in leukocytes-potential implications in obesity

The pituitary hormone prolactin (PRL), originally described for its role in lactation, has been implemented in over 300 functions and is produced by multiple cell types outside of the pituitary. Monocyte/macrophages in particular show robust expression of extra-pituitary prolactin (ePRL). While ePRL protein is identical to pituitary PRL and translated from the same gene, tissues outside the pituitary engage an alternative promoter to regulate expression. Many of the factors regulating this expression, however, remain unknown. Here we show that the adrenergic hormones epinephrine and norepinephrine induce PRL expression in the human monocytic cell line THP-1 at physiological concentrations. Furthermore, our experiments show the polarization state of differentiated macrophages can influence their response in vitro, with inflammatory M₁ macrophages-common in obese adipose-showing the highest levels of PRL expression compared to other macrophage types. Adrenergic hormones have a clearly defined role in adipocyte lipid metabolism, stimulating lipolysis through hormone sensitive lipase (HSL) induction. Meanwhile, PRL has been shown to stimulate lipogenesis. This highlights ePRL production as a possible factor in obesity. The overall balance of these two signals could play a critical role in determining overall lipid turnover/accumulation in adipose depots where large numbers of adipose tissue macrophages (ATMs) reside.