Hypothalamo-pituitary effects of RU486: inhibition of progesterone-induced hyperprolactinaemia

Monkeys given oestrogen priming at physiological levels for at least 1 week become hyperprolactinaemic upon the addition of physiological progesterone administration. Here, using RU486, we test whether that this oestrogen/progestin-induced hyperprolactinaemia results from classical progesterone actions at the hypothalamo-pituitary level. Blood samples were collected daily from study day 1-67. Each monkey (n = 2) received daily injections of 25 micrograms/kg oestradiol benzoate, i.m., on study days 5-60. Progesterone-filled silastic capsules (3 cm) were inserted on study day 14 and removed on day 53. On study days 39-45, each monkey received RU486 (25 mg/day, p.o.). Serum samples were stored at -20 degrees C until assayed for prolactin, oestradiol, progesterone and RU486 by radioimmunoassay. Hyperprolactinaemia was induced in all three monkeys upon insertion of progesterone capsules. Prolactin concentrations fell sharply during RU486 treatment to nadirs some 10-fold less than prior to RU486 treatment. The time series was modelled by the Box-Jenkins autoregressive-integrated moving average (ARIMA) method with progesterone producing a gradual increase in prolactin concentrations and RU486 producing a sudden decrease. Statistically significant effects of progesterone and RU486 were found. Thus, the addition of progesterone to an oestrogenized milieu significantly increased prolactin concentrations, and RU486 fully reversed this effect. This evidence indicates that the progesterone-induced hyperprolactinemia in an oestrogenized milieu results from classical progesterone effects.