TY - JOUR
T1 - Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro
AU - Coy, D. H.
AU - Labrie, F.
AU - Savary, M.
AU - Coy, E. J.
AU - Schally, A. V.
N1 - Funding Information:
of the Medical Research Council of Canada
PY - 1976
Y1 - 1976
N2 - The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50s) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.
AB - The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50s) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.
KW - antagonistic analogs
KW - cell culture
KW - LH
KW - pituitary
UR - http://www.scopus.com/inward/record.url?scp=0016987779&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0016987779&partnerID=8YFLogxK
U2 - 10.1016/0303-7207(76)90083-6
DO - 10.1016/0303-7207(76)90083-6
M3 - Article
C2 - 782958
AN - SCOPUS:0016987779
VL - 5
SP - 201
EP - 208
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 3-4
ER -
