Endocrine Abstracts (2011) 25 P277

Increased intensity of P450c17 protein expression in theca cells from polycystic ovaries

Fabio Comim, Kate Hardy & Stephen Franks

Imperial College London, London, UK.

Background/aims: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, being characterized by ovarian hyperandrogenism attributed to intrinsic overproduction by theca cells (TCs). Although previous reports pointed a higher stability and transcription of CYP17mRNA (Wickenheisser JK et al. 2006)1, few have examined (and none has quantified) P450c17 protein expression in TCs from PCOS ovaries. Therefore, the aim of this study is to quantify and compare protein expression of the steroidogenic enzymes in normal and PCOS ovaries employing the use of optical density measurements.

Materials and methods: We used quantitative immunohistochemitry (IHC) to examine expression of P450c17 and 3βHSD in archived ovarian tissue from PCOS (n=16) and normal women (n=10) obtained from the Histopathology Bank of St Mary’s Hospital, London. Overall, 82 follicles were classified as healthy (n=30) or atretic (n=52) based on previously established criteria (Brailly et al. 1981)2. Optical density measurements in theca cells were made using the software NIS-Elements AR 3.1(Nikon). Differences between groups were analysed using the Student t-test or Mann-Whitney test according with the distribution of data.

Results: Compared with normal ovaries, healthy follicles from PCOS had a higher proportion of theca cells strongly expressing P450c17 protein, PCOS: 0.40 (0.27–0.68) vs controls: 0.17 (0.07–0.37), (median (interquartile range); P=0.04, Mann Whitney test). Intensity of expression, (optical density arbitrary units) was also increased in PCOS: 0.82 (0.52–1.2) vs controls: 0.37 (0.28–0.57), P=0.04, (Mann Whitney test). No differences were seen in theca cell labelling for 3βHSD protein in terms of its optical density; PCOS (mean±S.D.): 0.16±0.008 vs controls 0.13±0.017, P=0.19 (Student’s t-test).

Conclusion: The increased proportion of P450c17 positive cells and the higher intensity of staining support the view that dysregulation of 17-hydroxlase/17-20 lyase activity in theca is a key abnormality in the aetiology of hyperandrogenism in PCOS.

2. Brailly S et al. JCEM. 1981 53(1): 128–134.

Acknowledgements: MRC, Capes Foundation, Dr R Parker (Univ Alabama,USA) (P450c17 Ab), Dr J L Mason (University of Edinburgh, UK) (3βHSDII Ab).

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