Effect of Naloxone on Luteinizing Hormone, Follicle-Stimulating Hormone, and Prolactin Secretion in the Different Phases of the Estrous Cycle*

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Abstract
It is becoming increasingly clear that the effects exerted by opioid agonists and antagonists on the release of gonadotropins and of PRL [prolactin] may vary according to the endocrine milieu. To investigate this issue further, female rats with a regular 4-day estrous cycle were injected s.c. with the opioid antagonist naloxone at different hours of the day, during each of the various days of the estrous cycle. The animals were killed 20 min after the s.c. administration of naloxone (2.5 mg/kg dissolved in 0.9% saline solution) at 1000 and 1600 h on the first and second day of diestrus and at 1000, 1200, 1400, 1600, 1800 and 2000 h on proestrus and estrus. Animals were killed by decapitation and trunk blood was collected and assayed for LH [luteinizing hormone] FSH and PRL. The data obtained from naloxone-treated animals were compared to those derived from controls injected s.c. with 0.9% saline solution and killed at the same time intervals. The s.c. injections of naloxone stimulated LH release in every phase of the estrous cycle; the magnitude of the responses was highly variable. Increases of the order of 700-1,000% were observed during the 2 days of diestrus, at 1000 and 1400 h of the day of proestrus, and at 1600, 1800, and 2000 h of the day of estrus. Much higher responses (of the order of 2,700-3,300%) were observed at 1600 h of the day of proestrus and at 1000, 1200, and 1400 h of the day of estrus. The LH response to naloxone appeared to be obliterated at 1800 and 2000 h of the day of proestrus. Serum levels of FSH and PRL were not affected by the treatment at any of the time intervals considered. Apparently, in normally cycling adult female rats, naloxone exerts a stimulatory effect on LH release during each day of the estrous cycle, the stimulatory effect of naloxone is minimal at the time of the spontaneous proestrous LH surge, and the effect of naloxone on LH release is, on the contrary, maximal just before the spontaneous proestrous LH surge and up to 1400 h of the day of estrus. The observation that naloxone does not affect FSH and PRL release underlines once more that the central mechanisms controlling LH, FSH and PRL secretion are different.