Prolactin receptor expression and prolactin-mediated effects in adipose tissue

Abstract

The aim of this study was to investigate the presence of functional prolactin receptors (PRLRs) in white adipose tissue of mice and humans, and the possible functions mediated via PRLRs. In mouse white adipose tissue, three PRLR mRNA isoforms, L-, S2-, and S3-PRLR, and L-PRLR protein expression were detected. In human subcutaneous abdominal and breast adipose tissue, four PRLR mRNA isoforms, L-, I-, S1a- and S1b-PRLR and PRLR proteins were detected. During lactation, mouse adipose tissue L-PRLR mRNA expression increased. Moreover, in the adipose tissue of prolactin (PRL)-transgenic mice with chronically elevated PRL levels, L-PRLR expression was also increased. Elevated serum testosterone increased L-PRLR expression in the adipose tissue of male mice. However, inhibition of progesterone in late gestation increased L-PRLR expression in the mammary gland but not in the adipose tissue. To investigate whether adipocyte PRLRs are functional, mouse adipocytes were cultured in vitro and the direct effects of PRL on suppressors of cytokine signalling (SOCS) expression and leptin secretion were investigated. PRL induced CIS mRNA expression in cultured adipocytes. Furthermore, PRL increased insulin-induced SOCS-3 expression significantly more compared to insulin alone. The insulin-induced leptin secretion was suppressed by PRL. In mouse adipose tissue in vivo, transient PRL stimulation induced SOCS-3, CIS and SOCS-2. In contrast, only SOCS-2 was increased in the adipose tissue after prolonged PRL exposure, as well as during pregnancy and lactation. In female PRL-transgenic mice, the retroperitoneal adipose tissue mass was reduced, serum leptin levels were elevated and adipose tissue resistin expression was unchanged compared to controls. However, resistin expression was increased in untreated male PRL-transgenics. Male PRL-transgenics have elevated serum testosterone and testosterone's role in regulating resistin was therefore studied. Resistin was increased in the adipose tissue of control mice with elevated testosterone, but not in castrated PRL-transgenic males, suggesting a role for testosterone in regulating resistin. In human adipose tissue cultured in vitro, the direct effect of PRL on lipoprotein lipase (LPL) activity was investigated and PRL inhibited the LPL activity in the human adipose tissue. In conclusion, this study demonstrates that there are functional PRLRs in white adipose tissue and PRL is an important regulator of adipose tissue metabolism in both humans and mice.