Androgen Regulation of Insulin Signaling in 3T3-L1 Induced Adipocytes
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Polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women, affects obese women disproportionately.1 This syndrome is characterized by hyperandrogenemia, cystic ovaries, and/or oligo/anovulation.2 Hyperandrogenic conditions such as PCOS are often associated with insulin resistance and hyperinsulinemia, particularly in obese women.3 However, it is unknown whether excess androgens play a direct role in the promotion of insulin resistance in obese females. We hypothesize androgens, independent from obesity, cause disruption of insulin signaling in adipocytes at the level of the androgen receptor (AR). Using the murine 3T3-L1 pre-adipocyte cell line, we assessed the effects of dihydrotestosterone (DHT; 10-6 M), a potent, non-aromatizable androgen, on insulin signaling in induced adipocytes. Identification of the role androgens may play in adipocyte insulin signaling will help elucidate the relationship between hyperandrogenemia and hyperinsulinemia and may provide a foundation for the development of new pharmaceuticals designed to target both hyperinsulinemia and hyperandrogenemia in obese female patients. We assessed mRNA transcript expression of forkhead box A1 (FOXA1), forkhead box O1 (FOXO1), insulin receptor (INSR), and protein kinase B isoform 2 (Akt2) relative to glyceraldehyde phosphate dehydrogenase (GAPDH) in cultured adipocytes and glucose present in cell culture media to determine how DHT may affect the insulin signaling in 3T3-L1 induced adipocytes. Our data revealed no significant difference in mRNA transcript expression of FOXO1, INSR, and Akt2 relative to GAPDH in control and DHT-treated 3T3-L1 induced adipocytes, and we found that FOXA1 could not be detected. Additionally, there was no significant difference in media glucose concentrations collected from wells containing DHT-treated and control 3T3-L1 induced adipocytes. While it is possible DHT does not alter insulin signaling in 3T3-L1 induced adipocytes, it recommended that additional replications of this experiment be completed in order to increase the statistical power.
Polycystic ovary syndrome
Bryson, Briana Danielle (2017). Androgen Regulation of Insulin Signaling in 3T3-L1 Induced Adipocytes. Undergraduate Research Scholars Program. Available electronically from