Localisation of adiponectin receptors in normal and polycystic ovaries
Fabio Comim, Sharron Stubbs, Kate Hardy & Stephen Franks
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. It is characterized by hyperandrogenism, which results primarily from excess androgen production by ovarian theca cells (TCs). Obesity contributes to androgen excess in PCOS and previous studies in vitro using bovine TCs have shown that adiponectin (production of which is inhibited in PCOS) is a repressor of P450c17 activity. However, little is known about expression of adiponectin receptors in the human ovary and no data to indicate whether adiponectin receptor expression is altered in PCOS.
Aims and methods: The aim of this study was to compare protein expression of adiponectin receptors 1 and 2 in normal and polycystic ovaries. We used specific antibodies to analyse, by immunohistochemistry, localisation of adiponectin receptors 1 and 2 in archived ovarian tissue from ovulatory PCOS (n=11), anovulatory PCOS (n=5) and normal women (n=10).
Results: Immunostaining for both ADIPOR1 and ADIPOR2 was observed in preantral and antral follicles of the human ovary, whether in PCO or control tissue. Expression of ADIPOR1 was more prominent in GCs whilst that of ADIPOR2 labelling was more intense in theca cells. Compared with normal ovaries, granulosa cells in primordial and transitional follicles from PCOS ovaries showed a lower proportion of positive staining for ADIPOR1 (P<0.03 Fishers exact test), whereas, in theca cells, there was a higher intensity of labelling for ADIPOR2 (P=0.03, Fishers exact test). However, no differences were distinguished when only ovaries from lean patients (BMI<25) were analysed.
Conclusion: We have reported, for the first time, expression of adiponectin receptor protein in the human ovary. ADIPOR1 receptors were more concentrated in GC layer and ADIPOR2 receptors in TC layer. There were no major differences between normal and polycystic ovaries in distribution or abundance of adiponectin receptors but the presence of these receptors in steroidogenic cells of the ovary suggest that circulating adipokines such as adiponectin can directly affect steroidogenesis and that any disturbance of adiponectin secretion (e.g. as a result of obesity/PCOS) may have implications for the pathogenesis of hyperandrogenism in PCOS.