Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity and insulin resistance. Since hyperandrogenism is a PCOS key feature, the aim was to evaluate the effects of androgen receptor activation in terms of continuously administration, beginning pre-pubertal, of either the non-aromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole (L), on ovarian morphology, as well as on the endocrine and metabolic status were investigated.
Methods: At 21 days of age, the rats were implanted subcutaneously with a pellet releasing DHT or L continuously during 90 days. Estrus cyclicity (vaginal smear), ovarian morphology, sex steroid and leptin concentrations, body composition (DEXA, MRI, and tissue dissection), mesenteric adipocyte size (computerized image analysis), and insulin sensitivity (euglycemic hyperinulinemic clamp) were examined.
Results: DHT induced polycystic ovaries (PCO) and anovulation in 75% of the rats. DHT rats also displayed increased body weight, fat mass and weight of individual abdominal fat depots, as well as enlarged mesenteric adipocyte size with a right shifted size distribution curve. Moreover, elevated leptin levels and insulin resistance were observed in DHT treated rats. Almost all L rats developed PCO morphology with similarity to human PCO, including hyperplastic theca cell layer, and anovulation. Hyperandrogenism and increased body weight without any body composition changes were other characteristics of the L group.
Conclusions: Typical PCO morphology was induced both by DHT and L treatment. In particular DHT treatment also resulted in metabolic disorders of the syndrome, while the endocrine features of the syndrome were mainly induced by L. Both models can therefore be concluded as suitable for investigation of different aspects of the human PCOS.