Effect of hyperprolactinemia and 2-BR-α-ergocryptine on neuroendocrine mechanism(s) for gonadotropin control

Abstract

The effect of hyperprolactinemia and of chronic treatment with 2-Br-α-ergocryptine (CB 154, 2.5 mg/kg s c, b.i.d., for 90 days) on hypothalamic centers for gonadotropin control was studied in intact or castrated (CX) Wistar/Furth (W/Fu) rats bearing a PRL-secreting tumor (MtTW5). CB 154 impeded the development of larger tumors in intact male and CX female rats but was ineffective in intact female and CX male rats. Irrespective of CB 154 treatment, plasma PRL at the end of the experiments was in the μg/ml range in all groups. Hypothalamic LH-RH in intact diluent-treated rats was significantly higher than in intact W/Fu controls (non tumor-bearing rats); castration completely antagonized the increased LH-RH content in the W/Fu male rats but was ineffective to modify the increased LH-RH content in the W/Fu female rats. CB 154 markedly decreased LH-RH content in W/Fu male controls, W/Fu male rats and in W/Fu intact and CX female rats. It was ineffective in CX W/Fu male rats and in the cycling W/Fu female controls. These data indicate that: 1) hyperprolactinemia increases hypothalamic LH-RH stores and blocks the discharge of LH-RH which follows castration; 2) CB 154 restores to normal the increased hypothalamic LH-RH stores of hyperprolactinemic rats, likely by promoting LH-RH discharge from the hypothalamus; 3) estrogens seem to counteract the effect of CB 154 on tumor growth.