Introduction: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders of premenopausal women. It is also the most frequent cause of female infertility and affects 6.58% of women in their reproductive age. Two out of three criteria diagnoses PCOS: oligo- or anovulation, clinical or biochemical signs of hyperandrogenism and polycystic ovaries at ultrasound. In addition, PCOS women frequently display features of the metabolic syndrome, such as abdominal obesity and type 2 diabetes mellitus. To investigate the possible interaction between ovarian dysfunction and the metabolic syndrome we determined the effect of androgens on differentiation, insulin sensitivity and lipolysis in 3T3-L1 adipocytes.
Material and methods: 3T3-L1 cells, a mouse white pre-adipocyte cell line, were stimulated with androgens during differentiation. Quantitative PCR was performed to measure expression levels of adipocyte marker genes. The effect of androgens on insulin sensitivity was analyzed by western blot analysis. Further, lipolysis was determined by measuring glycerol release.
Results: Our preliminary results showed that dihydrotestosterone (DHT) stimulated expression levels of early adipogenic markers (PPARγ and C/EPBα), while the expression of important marker genes for end stage adipogenesis (AP2, adiponectin and leptin) were inhibited. Insulin-stimulated glucose metabolism is mediated through insulin-induced Akt phosphorylation. Our experiments showed that DHT suppressed insulin-induced Akt phopshorylation, suggesting that DHT-treatment results in reduced insulin sensitivity. Insulin insensitivity is also reflected by an increased lipolytic activity. In contrast, basal levels of lipolysis were significantly decreased by 30% after 24 h stimulation with testosterone.
Conclusion: Our results show that DHT reduces insulin sensitivity, a crucial feature in the pathophysiology of PCOS and metabolic syndrome. Furthermore, our results suggest that androgens may program differences in adipocyte differentiation and/or function. Concluding, adipose tissue dysfunction, possible secondary to ovarian dysfunction, may be one of the causes of increased prevalence of metabolic syndrome in PCOS patients.
30 Apr - 04 May 2011
European Society of Endocrinology