Effect of prodynorphin-derived opioid peptides on the ovulatory luteinizing hormone surge in the proestrous rat

The objective of this study was to determine whether prodynorphin-derived opioid peptides could block the spontaneous luteinizing hormone (LH) surge and ovulation, and if so, whether this inhibitory action was mediated through κ-opioid receptors. Various doses of dynorphin peptides (dynorphin A_1–17, dynorphin A_1–8, dynorphin B, α- and β-neoendorphin) were infused into the brain through third-ventricle cannulae in rats between 1330–1800 h on proestrus. Each dynorphin peptide blocked the LH surge and ovulation in a dose-dependent manner. Dynorphin A_1–17 and A_1–8 were equally effective in producing these actions, and more potent than either dynorphin B or α- or β-neoendorphin. U50,488H, a specific κ-opioid receptor agonist, also blocked the LH surge and ovulation. When a mixture of five dynorphin peptides was infused intraventricularly, each at a dose that inhibited the LH surge, both the surge and ovulation were blocked. However, when norbinaltorphimine, a specific κ-opioid receptor antagonist, was coinfused with the mixture of dynorphin peptides, the LH surge and ovulation were fully restored. These results demonstrate that prodynorphin-derived opioid peptides, acting through κ-opioid receptors, can block the LH surge and ovulation. Dynorphin A_1–17 and A_1–8 are the most potent in this regard.