Gonadotropin releasing hormone activation is mediated by dimerization of occupied receptors.
A dinitrophenyl (DNP)-derivative of a gonadotropin releasing hormone (GnRH) antagonist was prepared by chemical modification of the epsilon amino group in position 6 of [D-pGlu1,D-Phe2,D-Trp3,D-Lys6]GnRH with 1-fluoro-2, 4-dinitrobenzene. The DNP-antagonist D-pGlu-D-Phe-D-Trp-Ser-Tyr-D-Lys(N epsilon-DNP)-Leu-Arg-Pro-Gly-NH2, retained high affinity binding to the GnRH receptor of pituitary membrane preparations and exhibited antagonistic activity when assayed in cultured pituitary cells. Both antibodies against DNP and their Fab fragments were able to bind the DNP-antagonist. However, only the addition of bivalent antibodies (and not the Fab fragments) converted the DNP-antagonist to an agonist. These results suggest that divalency is a critical factor in GnRH action.
D019297:2,4-Dinitrophenol; D000818:Animals; D000915:Antibody Affinity; D001667:Binding, Competitive; D001711:Biotransformation / Q000187:drug effects; D002064:Buserelin / Q000378:metabolism; D004140:Dinitrophenols / Q000276:immunology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011966:Receptors, LHRH
D004140:Dinitrophenols; D007140:Immunoglobulin Fab Fragments; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; C047472:LHRH, Phe(2)-N-epsilon-(2,4)-dinitrophenol-Lys(6)-; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D002064:Buserelin; D019297:2,4-Dinitrophenol