title: Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopausal women.
abstract: Progestogens and progesterone receptors (PR) may play an important role in increased breast proliferation following combined estrogen/progestogen hormone therapy, while androgens may counteract this effect. In 50 untreated healthy postmenopausal women and 48 untreated postmenopausal breast cancer patients, we measured serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estrone (E(1)) and adrenal androgens; and additionally, in the breast cancer patients, cortisol and corticosteroid-binding globulin and endocrine data related to breast proliferation (assessed using the Ki-67/MIB-1 monoclonal antibody) and PR levels (determined by enzyme immunoassay) in the breast cancer tissue. In the healthy women the percentage of MIB-1(+) cells showed significant negative correlations with serum levels of total T, calculated free T (fT) and the fT/E(1) ratio; while in the breast cancer patients PR content showed significant negative correlations with fT level, the fT/E(1) ratio and the T/SHBG ratio. No other correlations were found in any of the groups. Our findings in healthy women confirm previous reports of an antiproliferative effect of androgens in breast tissue and our finding in breast cancer patients suggests that this antiproliferative effect may be mediated via downregulation of PR.
authors.affiliation: Department of Woman and Child Health, Division for Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Hofling
authors.forename: Lars
authors.initials: L
authors.lastname: Löfgren
authors.forename: Eva
authors.initials: E
authors.lastname: von Schoultz
authors.forename: Kjell
authors.initials: K
authors.lastname: Carlström
authors.forename: Gunnar
authors.initials: G
authors.lastname: Söderqvist
mesh_terms: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry* / Q000473:pathology*; D002455:Cell Division; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000276:immunology; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D011374:Progesterone