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The Importance of Testes Function in Mouse Models of Cachexia
Author(s) -
Hardee Justin P.,
White James P.,
Puppa Melissa J.,
Aartun Johannes D.,
Narsale Aditi A.,
Sato Shu,
Carson James A.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1095.4
Subject(s) - cachexia , medicine , endocrinology , testosterone (patch) , androgen receptor , androgen , inflammation , receptor , weight loss , biology , prostate cancer , cancer , obesity , hormone
Hallmarks of cancer cachexia include chronic inflammation, insulin resistance and hypogonadism. Genetic and tumor implantation mouse models are methods used to study cancer cachexia. The purpose of this study was to explore the relationship between gonadal function and body weight (BW) loss in two mouse models of cachexia. Experiment 1: BALB/c mice were implanted with C26 tumor cells and monitored for 29 days. BW, testes weight, and circulating testosterone decreased in tumor bearing mice (p < 0.05). Experiment 2: Male ApcMin/+ (Min) mice were sacrificed at either 12, 14, or 20 weeks of age. Min BW, testes weight, and circulating testosterone decreased between 14 and 20 weeks of age (p <0.05). Testes expression of androgen receptor protein decreased, while Bax protein and pSTAT(Tyr705) increased between 14 and 20 weeks of age (p < 0.05). Testosterone levels and testes weight were correlated with BW loss in the Min mouse. Experiment 3: Male Min and C57BL/6 mice were treated with an IL‐6 receptor antibody or PBS control at 16 weeks of age for 2 weeks. Although cachexia decreased testes weight and circulating testosterone, IL‐6 receptor antibody administration attenuated these changes. In the C26 and Min mouse models of cachexia, decreased circulating testosterone appears to be an important regulatory event for the progression of the disease. Funded by NCI R01‐CA121249