Reversal of beta-endorphin-induced blockade of ovulation and luteinizing hormone surge with prostaglandin E2.

We examined the effects of intraventricular (Ivt) administration of beta-endorphin (beta E) on preovulatory LH release, ovulation, and the mechanism that may be involved in opioid action. Female rats were implanted with permanent cannulae in the third ventricle of the brain and were allowed to recover 4-day estrous cyclicity. Intrajugular cannulae were placed on the morning of proestrus. Thereafter, they received Ivt either saline (2 microliter) or beta E (10 micrograms/2 microliter) at 1300, 1430, and 1600 h. In addition, at 1600, 1700, and 1800 h, they were injected Ivt with either vehicle (cerebrospinal fluid or saline) or one of the following compounds: epinephrine (15.3 micrograms), norepinephrine (15.3 micrograms), or prostaglandin E2 (6 micrograms). Blood samples for LH measurements were taken 0, 10, 30, and 60 min after the additional injections at 1600 and 1700 h. beta E blocked the preovulatory LH surge and ovulation. Administration of the opiate receptor antagonist naloxone (2 mg/kg) reversed these effects. Epinephrine stimulated a small discharge of LH only after a second E injection in the beta E-treated rats, but this was insufficient to restore ovulation. On the other hand, prostaglandin E2 reversed the beta E blockade of the LH surge and ovulation. These studies suggest that beta E blocks ovulation and the LH surge primarily by suppressing either the influx or adrenergic expression of the spontaneous neurogenic stimuli responsible for the preovulatory LH discharge and not by evoking a general decrease in the secretory response of the LHRH neurons.