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The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 µl), 100 µg naloxone or 10 µg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 µg β-endorphin(1–27), a purported endogenous opioid antagonist.

In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 µg/l to less than 1 µg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 µg/l to undetectable levels, and neither saline nor naloxone affected LH secretion.

During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion.

These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect.

Journal of Endocrinology (1989) 122, 509–517

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