Evidence for the Involvement of Endogenous Opioids in the Inhibition of Luteinizing Hormone by Corticotropin-Releasing Factor*

Experiments were carried out in castrate adult male rats to further examine whether endogenous opioids are involved in CRF-induced suppression of LH secretion. Serum LH levels in rats castrated 5 days earlier were significantly reduced by intracerebroventricular administration of homologous (rat) CRF (0.02-2 nmol) within 30 min posttreatment; the effects of 0.02 nmol CRF lasted for at least 2 h, whereas those of 0.2 and 2 nmol CRF were evident for up to 6 h. Rats that received sc infusions of the opioid receptor antagonist naloxone (9.6 mg/kg.day) for 48 h before testing with 0.2 nmol CRF showed a significant reduction of the LH response to CRF. Rats that received two acute injections of naloxone (2 mg/kg, iv, 30 min apart) also showed an attenuated response to the LH-suppressive effects of CRF. In another experimental model where the opioidergic control of LH secretion is absent or masked, the long term castrate rat, there was also a marked attenuation of the LH-suppressing effects of CRF. Transient replacement of testosterone in long term castrates reinstated the inhibitory effects of CRF on LH secretion. A third experiment, in which short term castrates were pretreated with an opioid antibody and then with CRF, resulted in a significant reduction of the CRF-induced reduction of serum LH levels. These observations indicate that opioid receptor-mediated events play an important part in the actions of CRF on LH secretion. On the basis of our previous experiments in vitro, we propose that CRF stimulates the release of hypothalamic opioid peptides, which in turn inhibits the activity of LHRH neurons and, thus, LH secretion.