Developmental origin of polycystic ovary syndrome - a hypothesis.
Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.
Abbott
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Department of Obstetrics and Gynecology and Wisconsin Regional Primate Research Centre, University of Wisconsin, Madison 53715, USA.
Dumesic
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Franks
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D000728:Androgens / Q000096:biosynthesis / Q000502:physiology; D000818:Animals; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism; D008253:Macaca mulatta; D010049:Ovarian Diseases / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000196:embryology / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep
D000728:Androgens; D007328:Insulin; D007986:Luteinizing Hormone