title: Effect of Thyroid Function on MNU-Induced Mammary Carcinogenesis.
abstract: Mammary cancer is a disease that affects many women. Extensive research has been conducted to elucidate which variables are involved in the development of this cancer. Studies have highlighted thyroid function as a modulator of tumor growth and development. Thyroxine and 3,3',5-triiodothyronine are responsible for regulating the development, differentiation, homeostasis, and metabolism of cells in the body including mammary tissue. Thyroid hormones also have estrogen-like effects on mammary cancer cell growth by regulating the estrogen receptor. The present study was designed to determine whether medically induced hyperthyroidism increases the multiplicity, prevalence, and mammary tumor burden in rats; and to elucidate whether surgically induced hypothyroidism conversely attenuates the rate of mammary cancer cell growth. Female Sprague-Dawley rats were randomly divided into three groups (euthyroid-control, hyperthyroid, and hypothyroid). Hyperthyroidism was induced via oral administration of levothyroxine; whereas, hypothyroidism was induced by thyroidectomy. Mammary carcinogenesis was induced with a single intraperitoneal injection of N-methyl-N-nitrosurea (MNU). Rats were sacrificed at 38 weeks, and the mammary tumors were excised, fixed for histology and analyzed. Analysis included evaluation of malignancy and immunohistochemistry for ER. MNU-induced mammary carcinogenesis among the groups resulted in a significant difference in tumor burden. The hyperthyroid group had a statistically higher tumor burden than did the euthyroid group, and the hypothyroid group had no tumors of mammary tissue origin at 38 weeks. All excised mammary tumors were ER alpha negative. These data support the hypothesis that thyroid function is one of potentially many factors that contribute to modulation of MNU-induced mammary tumor growth.
authors.affiliation: 1 University of Wisconsin Madison School of Veterinary Medicine, Madison, WI 53706.
authors.forename: Mackenzie L
authors.initials: ML
authors.lastname: Vermey
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Marks
authors.forename: Monika G
authors.initials: MG
authors.lastname: Baldridge
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006980:Hyperthyroidism / Q000139:chemically induced* / Q000150:complications; D007037:Hypothyroidism / Q000150:complications*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000150:complications; D008770:Methylnitrosourea / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D013961:Thyroid Gland / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism / Q000633:toxicity
chemical_list: D008770:Methylnitrosourea; D013974:Thyroxine
keywords: MNU; estrogen receptor; mammary carcinogenesis; rat; thyroid hormones