Rf. Williams et al., HYPOTHALAMOPITUITARY EFFECTS OF RU486 - INHIBITION OF PROGESTERONE-INDUCED HYPERPROLACTINEMIA, Human reproduction, 9, 1994, pp. 63-68
Monkeys given oestrogen priming at physiological levels for at least 1
week become hyperprolactinaemic upon the addition of physiological pr
ogesterone administration. Here, using RU486, we test,whether that thi
s oestrogen/progestin-induced hyperprolactinaemia results from classic
al progesterone actions at the hypothalamo-pituitary level. Blood samp
les were collected daily from study day 1-67. Each monkey (n = 2) rece
ived daily injections of 25 mu g/kg oestradiol benzoate, i.m., on stud
y days 5-60. Progesterone-filled silastic capsules (3 cm) were inserte
d on study day 14 and removed on day 53. On study days 39-45, each mon
key received RU486 (25 mg/day, p.o.). Serum samples were stored at - 2
0 degrees C until assayed for prolactin, oestradiol, progesterone and
RU486 by radioimmunoassay. Hyperprolactinaemia was induced in all thre
e monkeys upon insertion of progesterone capsules. Prolactin concentra
tions 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 effec
ts of progesterone and RU486 were found. Thus, the addition of progest
erone to an oestrogenized milieu significantly increased prolactin con
centrations, and RU486 fully reversed this effect. This evidence indic
ates that the progesterone-induced hyperprolactinemia in an oestrogeni
zed milieu results from classical progesterone effects.