-
Views
-
Cite
Cite
R. P. MILLAR, R. C.DEL. MILTON, B. K. FOLLETT, J. A. KING, Receptor Binding and Gonadotropin-Releasing Activity of a Novel Chicken Gonadotropin-Releasing Hormone ([His5, Trp7, Tyr8]GnRH) and a D-Arg6 Analog, Endocrinology, Volume 119, Issue 1, 1 July 1986, Pages 224–231, https://doi.org/10.1210/endo-119-1-224
Close - Share Icon Share
Abstract
Receptor binding and gonadotropin-releasing activity was compared for mammalian GnRH, [Gin8]GnRH(chicken I GnRH), [His5, Trp7, Tyr8]GnRH (chicken II GnRH),[Trp7, Leu8]GnRH (salmon GnRH), and [D-Arg6] chicken IIGnRH.
The mean ED50 values for mammalian GnRH, chicken IGnRH, chicken II GnRH, and salmon GnRH in stimulating LHrelease from dispersed chicken pituitary cells were 0.27 nM, 0.28 nM, 0.055 nM, and 0.11 nM, respectively. The relative potenciesof the peptides compared in the same assay were 0.93, 1.0, 5.6,and 2.5. The ED50 values for chicken I GnRH, chicken II GnRH,and salmon GnRH in stimulating FSH release were 0.37 nM,0.034 nM, and 0.18 nM, and the relative potencies were 1.0,13.5,and 1.8. Chicken II GnRH was, therefore, more potent thanchicken I GnRH and mammalian GnRH in releasing LH andappeared to have an even greater relative FSH-releasing activitythan chicken I GnRH or mammalian GnRH. Introduction of DArg6into chicken II GnRH enhanced the activity of this analog 4- and 2-fold relative to chicken II GnRH in LH- and FSHreleasingactivity, respectively.
The ED50 values of mammalian GnRH, chicken I GnRH,chicken II GnRH, and salmon GnRH in releasing LH fromcultured sheep pituitary cells were 2.9 nM, 96 nM, 22 nM, and104 nM, respectively. The relative potencies were 1.0, 0.016,0.084, and 0.047. Introduction of D-Arg6 into chicken II GnRHenhanced activity 9-fold.
In a rat pituitary receptor binding assay the ED50 values of mammalian GnRH, chicken I GnRH, chicken II GnRH, andsalmon GnRH were 2.9 nM, 1480 nM, 19 nM, and 258 nM,respectively. [D-Arg6]Chicken II GnRH was 46 times more activethan the natural chicken II GnRH peptide.
The results show: 1) chicken II GnRH is more potent thanchicken I GnRH, which is equipotent with mammalian GnRHin releasing LH from chicken pituitary cells. Chicken II GnRHis even more potent at releasing FSH. 2) Salmon GnRH is alsomore potent than chicken I GnRH and mammalian GnRH instimulating gonadotropin release from chicken pituitary cells.appears, therefore, that Trp in the 7 position contributes to theenhanced activity of salmon and chicken II GnRH. 3) The lowactivity of chicken I GnRH, chicken II GnRH, and salmonGnRH in the sheep pituitary cell bioassay and rat pituitaryreceptor binding assay confirms that Arg8 in mammalian GnRHis important for activity. 4) Chicken II GnRH and salmon GnRHare more active than chicken I GnRH in the mammalian assaysystems, and thus, it appears that Trp7 enhances activity ofthese weak agonists. 5) D-Arg6 incorporation into chicken IIGnRH enhances activity in both the chicken and sheep pituitarybioassays but has a substantially greater effect in the latter.(Endocrinology119: 224–231, 1986)
