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 recently reported PRL receptor (PRLR) expression in mouse adipocytes and increased levels of PRLR expression in the adipose tissue of lactating and PRL-transgenic mice compared with controls. These results suggest PRLR-mediated effects in adipose tissue. However, to date most studies have been performed 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 suppressors 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), SOCS-3, and SOCS-2 mRNA and protein was analyzed using ribonuclease protection assay and immunoblotting, respectively. Ovine PRL induced CIS mRNA expression 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 and protein were all transiently expressed in adipose tissue obtained from female mice stimulated with oPRL (1 microg/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 increased in adipose tissue during pregnancy and lactation compared with that in wild-type virgin female mice. A possible reason for increased SOCS-2 expression after prolonged PRL exposure during lactation and in the PRL transgenes could be to restore the sensitivity of adipose tissue to PRL. In addition, the direct effect of PRL on leptin production was investigated in adipocytes cultured in vitro for 6 h. PRL inhibited insulin-induced leptin production in vitro. However, PRL had no effect on leptin production in the absence of insulin. In contrast, serum leptin concentrations were increased in PRL-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 transduction in adipose tissue.
Ling
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Department of Physiology, Goteborg University, SE 405 30 Göteborg, Sweden.
Billig
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D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins; D005260:Female; D017874:Immediate-Early Proteins / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology; D011247:Pregnancy; D011388:Prolactin / Q000235:genetics / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors
D016207:Cytokines; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D007328:Insulin; D020738:Leptin; D015735:Mifepristone; D011388:Prolactin; D011506:Proteins; D012333:RNA, Messenger; D054411:Receptors, Leptin; D011981:Receptors, Prolactin; D012097:Repressor Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; C515447:leptin receptor, mouse