Polycystic ovarian syndrome (PCOS) is one of the most prevalent forms of androgen excess and anovulatory infertility experienced by women, yet there is little understanding of the exact causes of this condition. Such a heterogeneous disorder is difficult to mimic in the laboratory and a suitable animal model has yet to be established. Antiprogesterone treatment, with mifepristone (RU486) in rats has been shown to induce endocrine and morphological features similar to those of PCOS (Uilenbroek, 1991; Sanchez-Criado et al, 1993), which show comparable responses to therapies used to treat women with PCOS (Ruiz et al, 1996). The aim of the present study was to investigate the effects of the antiprogesterone agent, ORG31710 (Mizutani et al., 1992), on reproductive function in female rats.

Twenty-one mature female hooded-Lister rats (250 ± 10g) were group housed under standard laboratory conditions and weighed daily. ORG31710 (10 & 20 mg/kg, s.c) or vehicle (olive oil, 1ml/kg s.c.) was administered once daily for 8 days (n = 7 per group). Stage of the oestrus cycle was histologically determined by vaginal lavage every day. On day 8, rats were sacrificed and ovarian, uterine and intra-abdominal fat weights recorded. Statistical comparisons were made by one-way ANOVA with post hoc Dunnett's t-test.

ORG31710 induced a persistent vaginal oestrus in all animals after day 2. There were no significant changes in body weights. ORG31710 significantly increased ovarian weights at both doses (p<0.05 - p<0.01, table 1) and significantly increased wet uterine weights at 20mg/kg (p<0.05, table 1).

Table 1. Effect of sub-chronic treatment with ORG31710 (10 & 20 mg/kg, s.c.) on uterine, ovarian and intra-abdominal fat weights over an 8-day treatment period

* p < 0.05 ** p < 0.01 compared with control values.

The present results showing that ORG31710 induced permanent oestrous and increased ovarian weights are in agreement with previous work of Ruiz and colleagues (1996) using ORG31710 and of Sanchez-Criado et al, 1993, using RU486. These results suggest that it may be possible to mimic certain aspects of PCOS in the rat. Such a model will greatly enhance our understanding of the pathophysiology of this most debilitating disease state.

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