Inhibition of mammary tumor growth in rats and mice by administration of agonistic and antagonistic analogs of luteinizing hormone-releasing hormone.
Experiments were undertaken with estrogen-dependent mammary carcinomas in rats and mice to determine the antitumor activities of agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). Chronic administration of the agonist [D-Trp6]LH-RH or of antagonist 1 ( [NAc-D-p-Cl-Phe1,2-Phe3,D-Arg6-D-Ala10]LH-RH) at doses of 25 and 50 micrograms/day, respectively, for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. The weight of the ovaries and serum progesterone levels in mice treated with [D-Trp6]LH-RH or antagonist 1 were also significantly reduced. In rats bearing the MT/W9A mammary adenocarcinoma, chronic administration of [D-Trp6]LH-RH at a dose of 25 micrograms twice a day or of antagonist 2 ( [NAc-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH) at a dose of 50 micrograms twice a day for 28 days significantly decreased tumor weight and volume. Chronic treatment with either [D-Trp6]LH-RH or antagonist 2 markedly diminished the weight of the ovaries and serum levels of both estrogen and progesterone. Serum luteinizing hormone was significantly decreased in rats treated with antagonist 2 but not in rats treated with [D-Trp6]LH-RH. There was a significant drop in serum prolactin levels in rats treated with [D-Trp6]LH-RH but not in those receiving antagonist 2. Regression of mammary tumors in rats and mice in response to chronic administration of [D-Trp6]LH-RH and the two antagonistic analogs of LH-RH suggests that these compounds should be considered for the development of a new hormone therapy for breast cancer in women.
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D017329:Triptorelin Pamoate
D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; C035819:LHRH, N-Ac-(4-Cl-Phe)(1,2)-Trp(3)-Arg(6)-AlaNH2(10)-; C037395:LHRH, N-Ac-(4-Cl-Phe)(1,2)-Phe(3)-Arg(6)-AlaNH2(10)-