Antioestrogen inhibition of oestradiol-induced alterations in hypothalamic noradrenaline turnover

Long-term (4-6 weeks) ovariectomized rats were injected with either oestradiol benzoate (OB; 20 micrograms s.c.) or monohydroxytamoxifen (MTAM; 0.2 mg i.p.) plus OB. Oestradiol benzoate was administered at 12.00 h on day 0 and MTAM was given immediately before OB, followed by further injections twice daily to maintain sufficiently high antioestrogen levels. When given alone, OB reduced the serum levels of LH during the morning (08.00-09.00 h) and afternoon (17.30-18.30 h) hours of day 3 after priming. The feedback actions of OB on LH release were accompanied by time-dependent alterations of noradrenaline turnover in the preoptic-anterior hypothalamic brain area (POAH). On day 3 after priming the noradrenaline turnover rate was reduced in the morning and increased in the afternoon. The increase correlated with an enhanced sensitivity of the LH secretory system to progesterone. The antioestrogen MTAM blocked the OB-induced sensitization of LH release to the stimulatory action of progesterone and interfered with the stimulatory long-term effect of oestradiol on hypothalamic noradrenaline turnover. The data strongly support the view that the oestrogen-induced afternoon increase of noradrenaline turnover in the POAH represents a prerequisite for the induction of LH surges. The stimulatory effect of oestradiol on hypothalamic noradrenaline turnover seems to be mediated by a classical oestrogen receptor mechanism.