Leptin signal transduction in the HP75 human pituitary cell line.
Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OBR). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS-3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary.
Tsumanuma
I
I
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Jin
L
L
Zhang
S
S
Bayliss
J M
JM
Scheithauer
B W
BW
Lloyd
R V
RV
D000236:Adenoma; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D010911:Pituitary Neoplasms; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C515448:LEPR protein, human; D020738:Leptin; D008894:Milk Proteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019000:Phosphotyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases