Endocrine Abstracts

PCOS is the most common endocrine disorder of premenopausal women. The in utero testosterone-treated ewe shares several key features with PCOS women (sub/infertility, multi-follicular ovaries, hypersecretion of gondotrophins and androgens) and, therefore, may be a useful animal model for this condition. In addition to reproductive abnormalities, PCOS women are at increased risk of hyperinsulinaemia and insulin resistance. The aim of this study was to determine if similar metabolic disorders were present in our PCOS model. Androgenised ewes (n=6) were generated by injecting pregnant sheep with 200mg per week testosterone propionate between day 30 and 90 of a 147 day gestation. Controls (n = 6) received no testosterone. The study was performed when animals were 18 months old (October 2004) when all controls, but none of the androgenised animals, were exhibiting ovarian cycles (determined from plasma progesterone concentrations). Androgenised animals were significantly heavier than controls (androgenised, 62.6 +/- 0.8; controls, 58.2 +/- 1.6 kg; p<0.05). Fasted animals received an i.v. injection of glucose (1 mMol/kg). Blood samples were collected on three occasions before and every 5 mins for one hour after glucose administration. Glucose concentrations (Glucometer) did not differ between the groups either before or after infusion. In contrast, baseline concentrations of insulin (RIA) were significantly higher (p<0.05) in the androgenised (13.6 +/- 2.4 microIU/ml) relative to the control group (6.7 +/- 0.9 microIU/ml). The total insulin response to glucose was also significantly higher (p<0.01) in androgenised (620.2 +/- 97.7 microIU/ml) compared to control ewes (313.8 +/- 33.2 microIU/ml). These data demonstrate that the in utero androgenised adult ewe is non-cyclic, significantly heavier, hyperinsulinaemic and insulin resistant compared with normal ewes. We suggest that this animal model may be useful in the study of the factors responsible for PCOS in women. (Supported by BBSRC and SHEFCA).