LH-releasing activity and receptor binding of pHGnRH 14-26 analogues.
The human gonadotropin-releasing hormone (GnRH) precursor consists of the GnRH sequence followed by a cleavage and amidation site and a 56-amino acid carboxyl-terminal extension (pHGnRH - precursor human GnRH) which has been shown to stimulate gonadotropin release. This activity has been localized to a decapeptide sequence (corresponding to pHGnRH 17-26) in its amino-terminal region using human pituitary cell cultures. To further characterize the structural features required for gonadotropin release, two analogues, [D-Ala17]pHGnRH 14-26 and [D-Trp22]pHGnRH 14-26, with D-amino acid substitutions inside and peripheral to this decapeptide sequence were chemically synthesized. pHGnRH 14-26 and the D-Ala17 analogue were inactive and GnRH, pHGnRH 14-36 and the D-Trp22 analogue stimulated luteinizing hormone release from cultured rat pituitary cells in a calcium-dependent, dose-responsive manner. Experiments and receptor binding studies with the active pHGnRH peptides in conjunction with GnRH or a GnRH antagonist suggest that the active pHGnRH peptides act through the GnRH receptor.
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011966:Receptors, LHRH / Q000378:metabolism*; D013329:Structure-Activity Relationship
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011966:Receptors, LHRH; C048414:GNRH precursor (14-26); D007986:Luteinizing Hormone