Inhibition of LH-release by synthetic analogues of LH-RH in rat pituitary cell culture.
Conditions for testing the inhibitory activity of synthetic analogues of LH-RH in monolayer cultures of rat pituitary cells were optimized. Nine synthetic derivatives of LH-RH were tested to evaluate their inhibitory dose50(ID50) values. The peptide antagonists tested included linear, branched-chain, dimeric and tetrameric derivatives of LH-RH, Ac-D-Phe1, D-Cpa2, D-Trp3,6-LH-RH (analogue V) was found to be the most effective competitive inhibitor of the series with an ID50 value of 6 x 10(-9)M in the presence of 10(-9) M LH-RH. The kinetics of the LH-RH-blocking action of two inhibitors were also studied. Both the linear (analogue I) and the dimeric (analogue VI) peptide showed immediate inhibition of HL-release. Prolonged inhibitory activity of the same two peptides was observed when cells were incubated with LH-Rh subsequent to preincubation with the inhibitors.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone