Evidence That a Decrease in Opioid Tone on Proestrus Changes the Episodic Pattern of Luteinizing Hormone (LH) Secretion: Implications in the Preovulatory LH Hypersecretion*

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Abstract
We have studied the LH secretion pattern evoked by diminution in the opioid tone produced by iv naloxone (NAL) infusion beteen 1100-1400 h on proestrus, the LH secretion pattern occurring spontaneously between 1430-1730 h on proestrus and the LH secretion pattern produced by exogenous LHRH administered either as a 10 ng/pulse at 20-, 30-, or 60-min intervals or infused continuously at a rate fo 30 ng/h between 1200-1700 h in rats given pentobarbital at 1100 h on proestrus. Infusion of 0.5 ng NAL/h raised plasma NAL levels to 200-300 ng/ml and augmented LH secretion, as evident by increments in pulse amplitude and frequency discharge to one every 37.5 min from an average of one every 75 min in saline-infused control rats. A 4-fold increase in circulating NAL levels, produced by 2 mg/h NAL infusion, further augmented the frequency of LH episodes to 30-33 min and induced a surge-like LH secretion pattern which resembled that seen on the afternoon of proestrus. Further analysis of the secretory pattern of the preovulatory LH surge (n = 7) showed LH pulses of increased amplitude during the basal phase (n = 4), ascending phase (n = 2), and plateau and descending phases (n = 3); in two rats the LH rise was steep, and no LH pulses were identified. A LHRH pulse (10 ng/pulse) delivered at 20- or 30-min intervals or continuous infusion of LHRH at a rate of 30 ng/h produced LH surges, with peak levels reaching the range seen on the afternoon of proestrus. Further, despite the fact that 10 ng LHRH/pulse at 20-min intervals reproduced a proestrous-type LH surge, only 40% of the LHRH pulses were followed by identifiable LH pulses were followed by identifiable LH pulses. Surprisingly, depsite the observations that NAL evoked robust LH episodes, the basal pattern of FSH secretion in these rats was not altered. These findings show that a decrease in opioid tone on proestrus accelerates episodic LH discharge to the range tht occurs after gonadectomy. A quantitative relationship between the degree of restraint on the opioid tone imposed by NAL and the magnitude of the LH response can be demonstrated. The evidence suggests that the preovulatory LH surge may occur in an episodic fashion and that it can be reproduced by LHRH delivered at a frequency rate of LH pulses seen in ovariectomized rats. Thus, collectively, these observations are in accord with the hypothesis that to evoke the preovulatory LH hypersecretion, the neural clock may curtail the inhibitory opioid tone on the afternoon of proestrus to permit accelerated episodic LHRH discharge at a rate close to that which normally occurs in ovariectomized rats.

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