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 kappa-opioid receptors. Various doses of dynorphin peptides (dynorphin A(1-17), dynorphin A(1-8), dynorphin B, alpha- and beta-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 alpha- or beta-neoendorphin. U50,488H, a specific kappa-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 kappa-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 kappa-opioid receptors, can block the LH surge and ovulation. Dynorphin A(1-17) and A(1-8) are the most potent in this regard.