The delineation of a decapeptide gonadotropin-releasing sequence in the carboxyl-terminal extension of the human gonadotropin-releasing hormone precursor.
The human gonadotropin-releasing hormone (GnRH) precursor consists of the GnRH sequence followed by a 59-amino acid carboxyl-terminal extension. A 56-amino acid peptide within this extension has been shown to stimulate gonadotropin release, and this activity has been localized to its amino-terminal region. A series of seven overlapping peptide fragments corresponding to the first 24 amino acids of the carboxyl-extension of the GnRH precursor were synthesized and tested for their ability to stimulate luteinizing hormone and follicle-stimulating hormone release from cultured human anterior pituitary cells. All active peptide fragments were found to incorporate the decapeptide sequence Asn-Leu-Ile-Asp-Ser-Phe-Gln-Glu-Ile-Val which is regarded as a minimal structural requirement delineated for gonadotropin-releasing activity. A further flanking sequence extending this active region from its carboxyl terminus was found to enhance gonadotropin-releasing activity although the flanking sequence itself was inactive. The gonadotropin release stimulated by the active peptides wa shown to be a dose- dependent, specific, and calcium-dependent phenomenon which occurred independently of the GnRH receptor on the pituitary gonadotrophs as a GnRH antagonist did not inhibit activity.
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology
D007202:Indicators and Reagents; D009842:Oligopeptides; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone