DIRECT ACTION OF GONADOTROPIN-RELEASING-HORMONE (LH-RH) ANALOG ON OVARY - AN ALTERNATIVE ACTING MECHANISM OF BUSERELIN

The mechanisms by which gonadotropin-releasing hormone (LH-RH) analogue buserelin exerts direct action on the ovary was investigated. The analogue inhibited the luteinizing hormone (LH)-induced increase of steroidogenesis by rat ovarian granulosa cells in a dose-dependent manner. The LH-RH analogue did not alter binding capacity and affinity of I-125-LH to granulosa cells, suggesting the involvement of post-receptor mechanism. Likewise, the analogue caused inositol trisphosphate (IP3) formation as a result of stimulated inositolphospholipid turnover. Half maximal effects of both steroidogenesis suppression and IP3 production occurred at 10 nM buserelin. These findings indicate that the inhibitory action of buserelin on granulosa cell function is mediated by IP3 (or calcium)-dependent mechanisms. Buserelin, in addition to its well-known action at pituitary level, exerts a direct inhibition of ovarian steroidogenesis at gonadal level without changes in gonadotropin receptors.