Synthesis and biological activity of [D-Trp6] chicken luteinizing hormone-releasing hormone.
An agonist of chicken hypothalamic luteinizing hormone-releasing hormone (cLH-RH), [D-Trp6] cLH-RH, was synthesized and tested for luteinizing hormone (LH)-releasing activity using dispersed chicken anterior pituitary cells, as well as for binding to rat anterior pituitary membrane receptors. cLH-RH and mammalian LH-RH (mLH-RH) gave identical dose-response curves in stimulating chicken LH release (ED50 = 1.6 and 1.8 X 10(-9) M respectively) and similar estimates of potency. The [D-Trp6] analogs of cLH-RH and mLH-RH stimulated LH release at lower doses (ED50 = 7.0 and approximately 7.0 X 10(-11) M respectively) and were approximately 20-fold more potent. In contrast to the activity in the chicken bioassay, cLH-RH bound to rat anterior pituitary membrane receptors with a much lower affinity than did mLH-RH and had a relative potency of 2%. [D-Trp6] cLH-RH was approximately 100-fold more potent than cLH-RH in the rat receptor assay while [D-Trp6] mLH-RH was 28-fold more active than mLH-RH. These data demonstrate that substitution of Gly6 of LH-RH with D-Trp enhances the LH release from chicken pituitary cells to a similar extent to that observed in mammals, and indicate that the approaches used to produce active LH-RH analogs in mammals are likely to be applicable to birds.
D000818:Animals; D001681:Biological Assay; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D008186:Luteolytic Agents / Q000138:chemical synthesis*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D013329:Structure-Activity Relationship; D017329:Triptorelin Pamoate
D007202:Indicators and Reagents; D008186:Luteolytic Agents; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone