HYPOTHALAMOPITUITARY EFFECTS OF RU486 - INHIBITION OF PROGESTERONE-INDUCED HYPERPROLACTINEMIA

Citation
Rf. Williams et al., HYPOTHALAMOPITUITARY EFFECTS OF RU486 - INHIBITION OF PROGESTERONE-INDUCED HYPERPROLACTINEMIA, Human reproduction, 9, 1994, pp. 63-68
Citations number
23
Categorie Soggetti
Reproductive Biology
Journal title
ISSN journal
02681161
Volume
9
Year of publication
1994
Supplement
1
Pages
63 - 68
Database
ISI
SICI code
0268-1161(1994)9:<63:HEOR-I>2.0.ZU;2-U
Abstract
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.