The Paradoxical Stimulatory Effect of Morphine on LH Secretion Is Dose-Dependent and Naloxone-Reversible

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Abstract
We previously observed that morphine stimulated luteinizing hormone (LH) secretion from ovariectomized rats when administered intravenously at a dose of 10 mg/kg body weight. The objectives of the present study were to determine: (1) if this paradoxical effect of morphine on LH secretion could be antagonized by naloxone; (2) whether β-endorphin also stimulated LH secretion under similar conditions; (3) what influence, if any, the ovaries have on the expression of this opiate-induced LH secretion, and (4) whether this paradoxical effect of morphine extended to prolactin (PRL) secretion. An intravenous injection of morphine, 10 mg/kg body weight, to ovariectomized rats acutely increased both plasma LH and PRL concentrations. The LH and PRL responses were completely antagonized by the concurrent administration of the opiate antagonist naloxone (1 mg/kg body weight). In contrast, morphine suppressed LH concentrations and had no effect on PRL levels when injected at a dose of 1.0 mg/kg body weight. Intravenous injections of β-endorphin, 1 mg/kg body weight, increased PRL concentrations to a level comparable to that observed following morphine, 10 mg/kg body weight, and produced a transient but insignificant inhibition of LH release. Intraventricular injections of much lower doses of β-endorphin resulted in a dose-dependent suppression of LH release and a dose-dependent stimulation of PRL release in ovariectomized rats. Intravenous administrations of morphine (10 mg/ kg), but not β-endorphin (1 mg/kg), to normal female rats resulted in a 2-fold increase in LH concentrations similar to that observed in ovariectomized rats, whereas both treatments similarly increased PRL concentrations. We conclude from these results that (1) morphine stimulation of LH secretion is dose-dependent and naloxone-reversible; (2) gonadal status does not appear to be an important factor, since this paradoxical effect of morphine was observed both in castrated and gonad-intact female rats: (3) β-endorphin and morphine affect LH and PRL secretion by different mechanisms, since none of the β-endorphin doses tried was able to stimulate LH secretion, even though these doses produced PRL responses that encompassed the PRL response to morphine. Furthermore, the relative potencies of β-endorphin and morphine with regard to PRL and LH secretion are different. β-Endorphin stimulated PRL secretion at a dose lower than that required to inhibit LH secretion, whereas morphine inhibited LH secretion at a dose lower than that required to stimulate PRL secretion. (4) The typical PRL response to morphine administration is maintained, even though the LH response was reversed. Based on these results, we believe that the hypothesis of both stimulatory and inhibitory opioid influences on LH secretion is tenable but would suggest an endogenous opiate other than β-endorphin as candidate.

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