title: A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells.
abstract: 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 interleukin- 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 (Ki ~ 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 interleukin- 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.
authors.affiliation: Boston Biomedical Research Institute (BBRI), Watertown, MA 02111, USA. gonzalezr@bbri.org
authors.forename: Ruben Rene
authors.initials: RR
authors.lastname: Gonzalez
authors.forename: Paul C
authors.initials: PC
authors.lastname: Leavis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000378:metabolism; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; C515448:LEPR protein, human; C507837:LIF protein, human; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D054411:Receptors, Leptin; D011994:Recombinant Proteins