Participation of both adrenergic and opioidergic systems in the negative feedback of adrenal progesterone on LH secretion.

It has been shown that adrenal progesterone plays an important role in regulating the negative feedback of oestrogen on luteinizing hormone (LH) release in ovariectomized and oestrogen-treated rats. The purpose of the present study was to determine whether adrenal progesterone modulation of LH secretion is mediated by adrenergic and opioidergic systems in ovariectomized and oestrogen-treated rats. Oestradiol benzoate (20 micrograms/rat) was given s.c. to ovariectomized rats on day 0. Control animals were injected with the vehicle alone. The specific adrenoceptor antagonists prazosin (10 mg/kg), idazoxan (100 micrograms/kg), metoprolol (10 mg/kg) or ICI 118,551 (200 micrograms/kg) were injected at 12.00 and 20.00 h on day 2 and at 08.00 h on day 3 to oestrogen-primed rats treated or not with RU486. Control animals were injected with saline. RU486 (10 mg/kg) was administered s.c. at 08.00 h on day 3 to oestradiol-treated animals receiving adrenoceptor antagonists or saline. Naloxone (2 mg/kg) was administered i.p. 30 min before blood-sampling to oestrogen-primed rats treated or not with RU486. All groups were blood-sampled at 13.00 and 18.00 h on day 3, and LH concentration was measured by radioimmunoassay. The administration of oestradiol to ovariectomized rats decreased serum LH levels at 13.00 and 18.00 h on day 3. Prazosin or idazoxan partially prevented the effect of oestradiol at 13.00 h, while metoprolol, ICI 118,551 or naloxone totally blocked the inhibitory effect of oestradiol on LH secretion; both adrenoceptor and opioid receptor antagonists also prevented the effect of oestrogen on LH concentration at 18.00 h. RU486 increased serum LH concentration at 18.00 h in oestrogen-primed rats to values higher than in ovariectomized control rats, with no effect at noon. The administration of prazosin to ovariectomized and oestrogen-primed rats treated with RU486 prevented this increase while the other adrenoceptor antagonists or naloxone increased serum LH concentrations at 18.00 h. The present study shows that RU486 switches the feedback of oestradiol on LH secretion from negative to positive in ovariectomized and oestradiol-primed rats, activating a stimulatory alpha 1-adrenergic pathway during the afternoon, and gives strong evidence about the participation of adrenal progesterone modulating neurotransmitter systems involved in the secretion of LH. It also supports the participation of endogenous opioid peptides in the negative feedback of oestradiol, suggesting that the inhibitory tone of endogenous opioid peptide is active regardless the action of adrenal progesterone.