Endocrine Abstracts (2004) 7 P34

The effect of DHT on the regulation of the renin angiotensin system in human abdominal subcutaneous adipocytes: implications for PCOS

AL Harte1, AE Fowler1, S Rodriguez-Cuenca2, R Chetty1, FFM Fisher1, LA Anderson1, P Roca2, S Kumar1, K Matyka1 & PG McTernan1

1Department of Medicine, University of Warwick, Coventry, UK; 2Department of Fundamental Biology and Health Sciences, University of Balearic Islands, Mallorca, Spain.

The renin-angiotensin system (RAS) is a key factor in the regulation of blood pressure and therefore its' blockade may reduce the vascular complications which arise with polycystic ovary syndrome (PCOS). Adipose tissue expresses all the components of the RAS system that includes the pre-prohormone angiotensinogen (AGT) and its' active metabolite angiotensin II (ANG II), which mediates vasoconstriction and electrolyte balance and as such may contribute to obesity associated hypertension in patients with PCOS. While central adiposity is clearly associated with this risk, limited studies to date have investigated the direct effects of testosterone on the production of AGT and ANG II. This present study investigated the role of dihydrotestosterone (DHT) concentration on both the expression of AGT and the secretion of ANG II in subcutaneous (Sc) abdominal fat from women (age 53.2plus/minus(SEM)8.3 years; weight 76.3plus/minus12.8kilograms). Isolated abdominal subcutaneous adipocytes (Sc ad; n=10) were treated with DHT (10-7Moles-10-9Moles) for 48 hr. Following treatment, protein was extracted and used to assess AGT by Western blot; while conditioned media were used to assess secretion of ANG II. Secreted bradykinin was also assessed. In Sc ad, DHT increased AGT in a concentration dependent manner (control: 1.0plus/minus(SEM)0.0; 10-9Moles: 1.26plus/minus0.07*;10-8Moles: 1.8plus/minus0.06***; 10-7Moles: 2.5plus/minus0.08***;***p<0.001; *p<0.05), ANG II levels were also increased in a similar pattern (control: 144plus/minus(SEM) 4.3 micrograms per millilitre;10-9Moles: 219plus/minus6.9micrograms per millilitre***; 10-8Moles: 332plus/minus18.6micrograms per millilitre***; 10-7Moles: 437plus/minus15.0micrograms per millilitre***). In summary, these present studies suggest that DHT may increase the local concentrations of AGT and ANG II in isolated adipocytes, which may contribute to hypertensive patients with PCOS. Further studies are required to characterise the mechanism by which DHT may alter ANG II levels in this system.