Effects of endogenous opioid peptides and opiates on luteinizing hormone and prolactin secretion in ovariectomized...

Adult female rats were implanted with permanent cannulae in the third ventricle of the brain and ovariectomized. 3 weeks later, blood samples were withdrawn every 5 min from intraatrial cannulae placed the previous day. After a control sampling period of 30 min, the rats received an intraventricular bolus injection of saline (2 microliter) or beta-endorphin (beta E; 10 micrograms); sampling was continued for an additional 2 h. Saline injection caused no effect on luteinizing hormone (LH) and prolactin (PRL) secretion. beta E stimulated PRL secretion within 5-10 min, the values peaked in the next 10 min. Thereafter, as PRL levels fell, a suppression of LH secretion became apparent. Inhibition of LH release started 20-35 min after beta E injection and lasted for 35-65 min. The antecendent PRL secretion was apparently not responsible for the observed delayed LH response, since blockade of PRL response with bromocriptine failed to affect the beta E-induced LH suppression. Further, continuous intraventricular infusion of beta E (5 or 10 micrograms/h) for 3 h markedly suppressed the amplitude and frequency of LH episodes in long-term ovariectomized rats. Bolus intraventricular injection of other endogenous opioid peptides and opiate receptor agonists produced different PRL and LH responses. Dynorphin (10 micrograms) similarly suppressed LH release but was only moderately effective in stimulating PRL. Leucine enkephalin (50 micrograms) stimulated LH and inhibited PRL release, while methionine-enkephalin (50 micrograms) selectively stimulated PRL release. The methionine-enkephalin analogs, FK-33824 (50 ng) and DALAMID (50 micrograms), evoked sequential PRL and LH responses similar to those seen after beta E injection. Interestingly, morphiceptin (a specific mu receptor agonist; 10 micrograms) markedly suppressed LH release, but only sparingly stimulated PRL release. Delta receptor peptide (a specific delta receptor agonist; 10 micrograms) selectively suppressed LH release. Bremazocine (a specific kappa receptor agonist; 0.5 mg/kg) administered intravenously suppressed LH release selectively. These studies show that of the four endogenous opioid peptides tested beta E was most effective in evoking sequential PRL and LH responses, and these effects may be mediated by either epsilon receptors or multiple opiate receptor subtypes; stimulation of kappa receptors by bynorphin or bremazocine suppressed LH release, and further studies would be needed to understand the mode of action of the two enkephalins and the delta opiate receptors in eliciting disparate PRL and LH responses.