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-Phe^1,2-Phe³,D-Arg⁶-D-Ala¹⁰]LH-RH) at doses of 25 and 50 μg/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 μg twice a day or of antagonist 2 ([NAc-D-p-Cl-Phe^1,2,D-Trp³,D-Arg⁶,D-Ala¹⁰]LH-RH) at a dose of 50 μg 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 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.