PCOS Forum

Research in Polycystic Ovary Syndrome Today and Tomorrow

Renato Pasquali; Elisabet Stener-Victorin; Bulent O. Yildiz; Antoni J. Duleba; Kathleen Hoeger; Helen Mason; Roy Homburg; Theresa Hickey; Steve Franks; Juha S. Tapanainen; Adam Balen; David H. Abbott; Evanthia Diamanti-Kandarakis; Richard S. Legro


Clin Endocrinol. 2011;74(4):424-433. 

In This Article

Specific Steroidogenic Enzyme Defects in PCOS

The aetiology of PCOS remains uncertain but intrinsic abnormalities in the synthesis and secretion of androgens are a plausible basis for the syndrome. There is clear evidence for constitutive hypersecretion of androgen by ovarian theca cells[14] but abnormalities of adrenal androgen production have also been implicated in the aetiology. It is therefore reasonable to pose the question 'Are specific primary enzyme abnormalities in the steroidogenic pathway an important cause of PCOS?'. On the basis of currently available evidence, the answer to this question is probably 'no'. Among plausible candidate genes in genesis of hyperandrognaemia are CYP17 (coding for P450c17, and the associated P450 reductase) and, because of evidence for a global increase in steroidogenic enzyme activity in polycystic ovaries (PCO) theca cells, CYP11a (P450scc).[15,16] To date, case–control and family-based studies have shown no clear evidence that variants in these genes (or for that matter, many others involved in steroidogenesis) contribute to the pathogenesis of PCOS. Recent work has focused on the metabolism of cortisol and adrenal androgens but, although specific enzyme defects may be associated with a PCOS phenotype (e.g. defects in cortisone reductase), the data from large association studies suggest that such defects are but a very minor contributor to the aetiology of PCOS.[16]

In addition, extraglandular synthesis of androgens, particularly in the adipose tissue, has been found to be involved in the pathophysiology of PCOS. They involve alteration in the activity of 11β-hydroxysteroid dehydrogenase[17] and both 5α-reductase and 5β-reductase.[10,18,19] Alterations in these enzyme systems, which are involved in peripheral cortisol metabolism, may in turn activate the neuroendocrine drive to support adrenal steroidogenesis and may partly explain the increased androgen production in specific subsets of women with PCOS.


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