The role of endogenous opioids in the ovulatory LH surge in mares

Removal of opioid inhibition of GnRH neurones is thought to be a critical event in generating the ovulatory surge in some species. In the present study, a nonsurgical technique was used to collect pituitary venous blood samples from eight mares every 0.5-1.0 min for 1 h before and after administration of the opioid receptor antagonist naloxone (0.2 mg kg(-1), i.v.), to investigate whether opioid inhibition is also important in mares. Jugular blood samples were taken at 10-15 min intervals. Mares were studied 0, 1 or 2 days before ovulation. Naloxone administration increased mean rates of GnRH (P < 0.01), LH (P < 0.001) and FSH (P < 0.001) secretion. The size of the increment did not vary with proximity to ovulation for any hormone. The amplitude of GnRH pulses rose after naloxone administration (P < 0.05) and the frequency and amplitude of LH pulses increased (frequency, P < 0.05; amplitude, P < 0.02), as did FSH pulse frequency (P < 0.001). Jugular LH and FSH concentrations tended to rise after naloxone administration; however, these changes were not significant. It is concluded that endogenous opioids inhibit GnRH secretion during the period of increasing LH concentration in the ovulatory surge, thereby slowing its rate of increase. It is postulated that treatment with opioid antagonists could be a physiological and non-antigenic way to accelerate and amplify the ovulatory surge in the breeding season. Although a single injection of naloxone is inadequate to do this, it is likely that continuing antagonism, for example with a long-acting, orally-active analogue such as naltrexone, would maintain increased GnRH and LH secretion for sufficient time to raise peripheral LH concentrations and decrease the time until ovulation.