Reference : Antagonistic properties of human prolactin analogs that show paradoxical agonistic ac...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Antagonistic properties of human prolactin analogs that show paradoxical agonistic activity in the Nb2 bioassay
Goffin, Vincent [INSERM unit 344 > > > >]
Kinet, Sandrina [Université de Liège - ULiège > > > >]
Ferrag, Fatima [INSERM unit 344 > > > > > >]
Binart, Nadine [INSERM unit 344 > > > > > >]
Martial, Joseph mailto [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Kelly, Paul A [INSERM unit 344 > > > > > >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
[en] Animals ; Binding Sites ; Biological Assay ; Cell Line ; Humans ; Prolactin/*analogs & derivatives/pharmacology ; Rats ; Receptors, Prolactin/*agonists/*antagonists & inhibitors ; Species Specificity
[en] Based on the assumption that the prolactin receptor (PRLR) is activated by PRL-induced sequential dimerization, potential human PRL (hPRL) antagonists were designed that sterically interfere with binding site 2. We previously reported the unexpected agonistic properties of these hPRL analogs in the rat Nb2 bioassay (Goffin, V., Struman, I., Mainfroid, V., Kinet, S., and Martial, J. A. (1994) J. Biol. Chem. 269, 32598-32606). In order to investigate whether such paradoxical agonistic behavior might result from characteristic features of the Nb2 assay (e.g. species specificity), we transfected in the same cell system the cDNA encoding the PRLR from rat or human species along with reporter genes containing PRL-responsive DNA sequences. We characterized the agonistic, self-antagonistic and/or antagonistic effects of wild type rat PRL, wild type hPRL, and three hPRL analogs, mutated either at binding site 1 or at binding site 2. Our results clearly show that the agonistic/antagonistic properties of PRLs are species-specific. We thus propose different models of receptor activation, depending on the relative affinities of each hormonal binding site, which is directed by species specificity. Finally, this is the first report of hPRL binding site 2 analogs showing antagonistic properties on human and, to a lesser extent, rat receptors.

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