title: Additional effects of medroxyprogesterone acetate on mammary tumors in oophorectomized, estrogenized, DMBA-treated rats.
abstract: Although hormone replacement therapy not only relieves vasomotor symptoms but also reduces cardiovascular disease and osteoporosis, long-term estrogen therapy increases the risk of endometrial and/or mammary cancer. We investigated the effects of conjugated estrogens with or without medroxyprogesterone acetate in oophorectomized, 7,12-dimethylbenz(a)anthracene-treated rats. Chemically induced mammary carcinogenesis was completely suppressed by the simultaneous oophorectomy, but conjugated estrogens replacement with or without medroxyprogesterone acetate markedly stimulated mammary carcinogenesis in the ovariectomized rats. The chronic administration of conjugated estrogens and medroxyprogesterone acetate markedly reduced the activities of thymidylate synthetase and thymidine kinase and bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These results indicate that the treatment using conjugated estrogens with or without medroxyprogesterone acetate may promote the mammary carcinogenesis in postmenopausal women but the chronic administration of medroxyprogesterone acetate may alter the development of established mammary cancer.
authors.affiliation: Department of Endocrinology, Tokyo Medical and Dental University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Kudo
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Mitamura
authors.forename: S
authors.initials: S
authors.lastname: Sassa
authors.forename: K
authors.initials: K
authors.lastname: Kuwa
authors.forename: Z
authors.initials: Z
authors.lastname: Chun
authors.forename: S
authors.initials: S
authors.lastname: Yoshimura
authors.forename: M
authors.initials: M
authors.lastname: Maemura
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: H
authors.initials: H
authors.lastname: Shinoda
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000097:blood*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D010052:Ovariectomy; D017698:Postmenopause; D011374:Progesterone / Q000097:blood*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013937:Thymidine Kinase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D011374:Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D017258:Medroxyprogesterone Acetate; D013940:Thymidylate Synthase; D013937:Thymidine Kinase