PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro

PRL has been reported to regulate fat metabolism in several species. We rec ently reported PRL receptor (PRLR) expression in mouse adipocytes and incre ased levels of PRLR expression in the adipose tissue of lactating and PRL-t ransgenic mice compared with controls. These results suggest PRLR-mediated effects in adipose tissue. However, to date most studies have been performe d in vivo, and it is unclear whether PRL has direct effects on adipocytes. The PRLR belongs to the cytokine receptor family, and a family of suppresso rs of cytokine signaling (SOCS) was recently identified. The present study was performed to investigate whether PRL has direct effects on adipocytes. The expression of cytokine-inducible SH2-domain-containing protein (CIS), S OCS-3, and SOCS-2 mRNA and protein was analyzed using ribonuclease protecti on assay and immunoblotting, respectively. Ovine PRL induced CIS mRNA expre ssion and a combination of oPRL, and insulin induced SOCS-3 mRNA expression in adipocytes cultured in vitro for 0-240 min, demonstrating PRLR-mediated direct effects in these cells. Furthermore, CIS, SOCS-3, and SOCS-2 mRNA a nd protein were all transiently expressed in adipose tissue obtained from f emale mice stimulated with oPRL (1 mug/g BW) for 0-24 h. In adipose tissue of female mice with endogenously high PRL levels, PRL-transgenic mice, only SOCS-2 expression was increased. The level of SOCS-2 mRNA was also increas ed in adipose tissue during pregnancy and lactation compared with that in w ild-type virgin female mice. A possible reason for increased SOCS-2 express ion after prolonged PRL exposure during lactation and in the PRL, transgene s could be to restore the sensitivity of adipose tissue to PRL. In addition , the direct effect of PRL on leptin production was investigated in adipocy tes cultured in vitro for 6 h. PRL inhibited insulin-induced leptin product ion in vitro. However, PPM had no effect on leptin production in the absenc e of insulin. In contrast, serum leptin concentrations were increased in PR L-transgenic females compared with control mice. In conclusion, our results demonstrate functional PRLRs in mouse adipocytes and suggest a role for CIS, SOCS-3, and SOCS-2 in regulating PRL signal tr ansduction in adipose tissue.