title: Human chorionic gonadotropin inhibits N-Methyl-N-nitrosourea-induced mammary carcinoma growth in female Lewis rats.
abstract: Human chorionic gonadotropin (hCG), a hormone produced by the placenta, is essential for maintaining pregnancy. The tumor-suppressive property of hCG against palpable N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinomas was examined. A single intraperitoneal injection of 60 mg/kg MNU was administered to female Lewis rats. When the MNU-induced mammary tumors reached a palpable size (≥ 1 cm in diameter), 0, 100, or 300 IU hCG were intraperitoneally injected 5 times per week for 4 weeks (a total of 20 injections). At the end of the treatment period, the 300 IU hCG treatment had significantly suppressed the growth of MNU-induced mammary carcinomas as compared to the sham treatment. The lower dose of hCG (100 IU) did not exert a significant effect. Final tumor volume and tumor wet weight, respectively, were as follows: sham-treated, 8151.3 ± 1367.1 mm(3) and 6011.3 ± 1042.2 mg; 100 IU hCG, 7480.6 ± 2011.2 mm(3) and 5613.5 ± 1142.0 mg; and 300 IU hCG, 3925.0 ± 875.3 mm(3) and 3482.4 ± 817.3 mg. Serum estrogen and progesterone levels were markedly elevated to pregnancy levels in 300 IU hCG-treated animals, while serum hCG levels remained low, resulting in significantly increased ovarian and uterine weights with multiple corpora lutea in the ovary and cystically dilated endometrial glands. Immunohistochemical studies revealed that almost all hCG-treated mammary carcinoma cells expressed estrogen and progesterone receptors, whereas luteinizing hormone/chorionic gonadotropin receptor was barely detectable. In conclusion, 300 IU hCG treatment for a short duration (4 weeks) suppressed the growth of overt and palpable MNU-induced mammary carcinomas. The mechanism of action may be through accelerated ovarian steroid secretion with the elevation of estrogen and progesterone levels to those in pregnancy.
authors.affiliation: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. yurit@takii.kmu.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lai
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008770:Methylnitrosourea; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D011374:Progesterone / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D047368:Tumor Burden / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006063:Chorionic Gonadotropin; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea