期刊
ENDOCRINE
卷 21, 期 2, 页码 185-195出版社
SPRINGER
DOI: 10.1385/ENDO:21:2:185
关键词
leptin peptide antagonist; leptin receptor; interleukin 1; leukemia inhibitory factor; endometrial receptivity; implantation
in this article we show that rabbit endometrial cells express leptin receptor and that human leptin triggers phosphorylation of signal transducer and activator of transcription 3 and up-regulates the expression of interieukin-1 receptor type I as was previously found in human endometrial cells. Interestingly, leptin also upregulates the secretion of leukemia inhibitory factor and expression of its receptor by rabbit endometrial cells. Analysis of a structural model of the leptin-leptin receptor complex suggested that helices I and III of the human leptin structure were likely sites of interaction with the cytokine binding domain of leptin receptor. Accordingly, we synthesized a peptide (LPA-2) comprising helix III (residues 70-95) and investigated its ability to inhibit leptin receptor function. The effects of LPA-2 were assayed in rabbit endometrial cells, and an antileptin receptor antibody and a scrambled version of LPA-2 were used as positive and negative controls, respectively. LPA-2 binds specifically and with high affinity (K-i similar to 0.6 x 10(-10) M) to leptin receptor and is a potent inhibitor of its functions in rabbit endometrial cells. Because leukemia inhibitory factor and interieukin-1 have been implicated in embryo implantation, our results raise the possibility that the LPA-2-induced inhibition of leptin receptor may be exploited to study the actions of leptin in endometrium and in other tissues under conditions characterized by abnormal leptin production.
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