Callahan Phyllis

Miami University

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Helaine M. Alessio

Miami University

Angela M. Snedden

Miami University

Ann Hagerman

Miami University

Natalie B. Schweitzer

Miami University

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Miami University

Nationwide Children's Hospital

Google (United States)

State University of Physical Education and Sport

National Institute on Aging

University of Maryland, College Park

University Hospital of Geneva

University of Geneva

University of Minnesota Medical Center

University of Mississippi

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Influence of Tumor Promoting Prolactin, Energy Balance, and Gene Expressions on Spontaneous Tumor Development in Laboratory Animals

Medicine & Science in Sports & Exercise (2006)

Helaine M. Alessio Natalie B. Schweitzer Angela M. Snedden Callahan Phyllis Ann Hagerman

Tumor growth is impacted by energy balance, a tumor-promoting hormone, prolactin, and genetics. Physical inactivity can affect energy imbalance and blood prolactin concentration, which could ultimately modify gene expression associated with tumor regulation. Spontaneous tumors occur in 45-71% of Sprague-Dawley (SD) laboratory rats, yet few studies have considered the potential impact of the inherent sedentary condition of a standard cage on tumorigenesis. Tumor profiles, microarray analyses, and tumor promoting hormone prolactin were compared to determine how residing in a standard cage affects tumor development. Female SD rats were sorted into 1. cage with no outside activity (SED), 2. twice-weekly, one hour physical activity in large box (PA), and 3. regular voluntary running wheel exercise (EX) groups. SED had higher tumor number and size throughout most of their lifespan compared with EX. PA had tumor profiles similar to SED. Higher tumor burden (54%) in SED vs. EX (38%), although falling in the range of previous studies, may be abnormally high due to the sedentary setting of a standard cage. At 16 months, SED tumors included thyroid carcinoma, malignancy, mammary fibroadenoma, cystadenoma, and granuloma when compared with benign mammary gland cysts that were most common in EX. Eight cardiac genes related to tumors were down-regulated in SED vs. EX (i.e. Rab40c, Lyn, Rab5b, Mycn, Tnfsf13, Fyn Brca1, and LOC291530), and five were up-regulated (i.e. Tnfrsf4, C1qtnf1, Tnfsf9, Dlc1, and RGD:619831). Prolactin levels were highest in SED at ages 6 and 12 months (p<0.05), after which age-associated hyperprolactinemia occurred. In conclusion, when compared with animals that had access to exercise, animals housed in standard cages had a larger number and size of tumors that included malignancy, as well as higher prolactin levels, lower energy intake,lower energy expenditure,and thirteen different tumor-associated gene expressions.

sed

Pituitary Tumors

10.1249/00005768-200611001-00032

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