Comparison of different agonists and antagonists of luteinizing hormone-releasing hormone for receptor-binding ability to rat pituitary and human breast cancer membranes.
A sensitive multipoint assay capable of measuring receptors for LHRH and its analogs using 5-10 micrograms membrane protein/incubation tube was used to determine binding characteristics of different agonists and antagonists of LHRH in membranes of male rat pituitary and human breast cancer specimens. This method also permitted Scatchard analysis of the receptor binding in pellet fractions of human breast cancer biopsies remaining from estrogen and progesterone receptor assays. The potent agonist [D-Trp6]LHRH bound to at least two classes of receptor sites, one with high affinity and one with low affinity in both rat pituitary and human breast cancer samples. The analysis of displacement curves of LHRH by agonists and antagonists showed that LHRH also bound to two classes of receptor sites in pituitary and one receptor site with lower affinity in human breast cancer membranes. Among the antagonists synthesized in our laboratory, SB-030, SB-077, SB-088, and SB-090 appeared to be the most potent in displacing labeled [D-Trp6]LHRH and showed the highest binding affinity to the pituitary and breast cancer membranes. Labeled antagonists showed somewhat less affinity to membranes of pituitaries and human cancers than the agonists and bound to only a single class of receptor population. Both agonists and antagonists were able to bind to membranes of human breast cancer samples, and some antagonists were very potent in this respect. Certain LHRH agonists or antagonists could be capable of exerting direct inhibitory effects on breast cancers depending upon the presence and characteristics of LHRH receptors.
Fekete
M
M
Endocrine, Polypeptide, and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana 70146.
Bajusz
S
S
Groot
K
K
Csernus
V J
VJ
Schally
A V
AV
D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis; D011966:Receptors, LHRH / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000032:analysis; D013329:Structure-Activity Relationship
D011960:Receptors, Estrogen; D011966:Receptors, LHRH; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone