Further studies on possible dynorphin involvement in the ovulatory luteinizing hormone surge in the proestrous rat.

A decrease in inhibitory tone of endogenous opioid peptide on the afternoon of proestrus is one event underlying generation of the ovulatory luteinizing hormone (LH) surge, since premature removal of this inhibitory tone (i.e., disinhibition) results in an early onset of the surge. Our laboratory demonstrated that blockade of kappa-opioid receptors in the medial preoptic area (MPOA) advanced the onset of the LH surge on proestrus. Since dynorphin is the endogenous ligand for the kappa-opioid receptor, the present studies examined the possible role of dynorphin in this disinhibition response. 1) Neutralization of endogenous dynorphin peptides, by push-pull perfusion of the MPOA with antibodies specific for dynorphin A1-17 or A1-8 from 1030-1355 h on proestrus, tended to prematurely advance the increase in plasma LH levels normally occurring on this day of the estrous cycle. Although this increase was not statistically significant when compared with controls, plasma LH levels in two antibody-treated rats were sufficiently elevated to cause full ovulation, a response that did not occur in controls. These data suggest that dynorphin A1-7 and A1-8 might have a role in the MPOA, although a minor one, in suppressing LH secretion early on proestrus. MPOA levels of prodynorphin mRNA decreased at 1700-1800 h on proestrus when plasma LH levels were high, compared with values at 1300-1400 h when plasma LH levels were low. This change did not occur on diestrous d 1 when there was no LH surge. 2) MPOA levels of kappa-opioid receptor mRNA did not change on proestrus or diestrous d 1. These results suggest that a reduction in prodynorphin gene expression on the afternoon of proestrus may be one event involved in a possible decrease in dynorphin inhibitory tone on the ovulatory LH surge-generating signal.