Transcript – Dihydrotestosterone Differentially Regulates Predictors of T Cell Function in Visceral and Subcutaneous Adipose Tissue of Female Mice

Our T3 project assesses the ability of potent androgens to modulate adipose tissue, fatty acid turnover via inflammatory cells and micro RNA control. Collaborators on this project include Annie Newel-Fugate, Stephen B. Smith and Mahua Chaudry. Polycystic ovary syndrome affects 10 percent of reproductive age women and is coupled with multiple metabolic abnormalities, including increased amounts of intra-abdominal or visceral adipose tissue and insulin resistance. While the antigen testosterone is known to modulate fatty acid, turnover and adipocytes, the mechanisms by which it accomplishes this are unknown. Additionally, adipocytes can traumatize testosterone into the estrogen estradiol. Therefore, the effects of testosterone on fatty acid turnover in these cells could be due to androgen or estrogen mediated effects.

Our team decided to use dihydrogen testosterone or DHT, which is a potent androgen, to truly evaluate the effect of insurgents in white adipose tissue of female mice. Our hypothesis is that short term dihydrogen testosterone administration to sexually mature leading female mice would cause increased inflammation and modulation. microRNAs known to be related to obesity in the subcutaneous adipose tissue. Specifically, we found that our treatment caused elongated Easter cycles and increased serum. Dihydrogen testosterone concentrations in DHT treated mice to 16- to 17-fold that of control mice. Additionally, dihydrogen testosterone, or DHT, caused down regulation of cytokine transcripts and mesenteric and up regulation of cytokine transcripts in subcutaneous white adipose tissue pathway. Analysis of our cytokine transcript data demonstrated that pathways affected include one A.H. to activation pathways t helper cell differentiation pathways and beat to t cell communication pathways. The moment we are looking at relative transcript levels of microRNAs downstream of these pathways, as well as evaluating B and T cell abundance and functionality in the wide adipose tissue of our treated animals. These data suggest that androgens and females may in fact alter ability to mount a normal immune response, particularly in the adipose tissue environment, and may be related to metabolic abnormalities seen in this tissue and the results that are seen systemically in the body of females with high androgen concentrations.

We’d like to thank the Texas A&M President’s Excellence Fund for our funding, as well as all of our co-authors.