156. EFFECTS OF ALBENDAZOLE ON OVARIAN OESTROGEN SYNTHESIS IN THE RAT

Abstract

Albendazole is a drug commonly used for treatment of helminth infestation in human and livestock populations. Recent studies show that albendazole reduces ovarian follicular fluid oestrogen levels in sheep¹, but the mechanism involved is unknown. The aims of this study were to determine whether albendazole exerts similar effects on ovarian oestrogen levels in the rat, and to assess the effects of albendazole on expression of key steroidogenic genes in the rat ovary. Oestrus cycles were continuously monitored in Wistar rats by vaginal smears. Commencing at proestrus, albendazole was administered for 12 days in drinking water (approximate dose 15 mg/kg/day). Plasma and whole ovaries were collected on the fourth proestrus (1500–1600h). A second group of rats were treated similarly except that pseudopregnancy (PSP) was induced by mating with a vasectomised male at the second proestrus. Plasma and the non-luteal ovary were collected on day 8 of PSP. Oestradiol was extracted from plasma and ovaries with ethyl acetate and concentrations measured by a chemiluminescent assay. Expression of steroidogenic acute regulatory protein (StAR), P450 side chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), aromatase and 20α-hydroxysteroid dehydrogenase (20α-HSD) mRNAs were measured by RT-PCR. Oestrus cyclicity, ovarian weight and mating behaviour were all unaffected by albendazole in cycling and PSP rats, although as expected levels of oestradiol were lower in PSP. In ovaries of cycling rats albendazole did not affect oestradiol concentrations but reduced ovarian P450scc mRNA expression (by 65%; P=0.024) and there was a trend for an increase in 3β-HSD (P=0.09) and aromatase expression (P=0.12). Expression of the other steroidogenic genes was unaffected and no changes in gene expression were observed in PSP rats. In conclusion, albendazole treatment reduced ovarian P450scc in cycling rats but did not inhibit ovarian oestradiol synthesis or reproductive function.