Abstract

The PCOS is a common disorder that affects approximately 5 million of women of reproductive age in the United States and it is estimated that the cost in health to identify and treat these patients is approximately of 4 billion dollars annually. The prevalence of this disorder is the same in different countries, therefore, although the cost for the public or private health system in Chile is not known, but it may also be very high. The causes of PCOS are not well identified. Some studies suggest that it would be an alteration with a strong genetic component, while others suggest that factors from the environment, either intra or extrauterine, would play an important role. It is currently considered that PCOS is a family endocrine-metabolic disturbance with alterations associated with diabetes type 2. Since this syndrome entails a high demand on health resources, strategies aimed to prevent or at least to delay its start, is a must in order to implement preventive measures. This is likely to obtain because the early onset of the symptoms, which permits to identify these patients at an early age, allowing to establish early preventive measures. In this line of thinking, urderstanding the complex mechanisms in the development and ontogeny of the PCOS that may probably begin to operate during fetal life and or the triggering at postnatal life, and claryfing the contribution of testosterone on this, will help to provide preventive measures. In this regard, experimental models of PCOS are of evident value because of the boundary implicit in experimenting with humans due to ethical considerations. In this research proposal, fetal programming by testosterone would be the driving motif of the origin of PCOS in humans using an animal model already validated by studies from our laboratory as well as from others. We will define if the insulin resistance (IR), main metabolic feature of PCO, is present at the fetal stage in females, using molecular markers in insulin sensitive tissues. Thereafter, the contribution of T to the IR in females with or without oopheroctomy will be examined using a validated intravenous glucose tolerance test (IVGTT) and markers of IR in insulin sensitive tissues (muscle and adipose tissue). Moreover, the beta cell dysfunction could also have a main role in the IR. We will demonstrate that T is the main contributor to the IR in females and that the exposure to further testosterone exposure (like it happens when young women exhibits the syndrome), aggravates the already existing IR.