Piva F, Maggi R, Limonta P, Motta M, Martini L
Endocrinology. 1985 Aug;117(2):766-72. doi: 10.1210/endo-117-2-766.
It is becoming increasingly clear that the effects exerted by opioid agonists and antagonists on the release of gonadotropins and of PRL may vary according to the endocrine milieu. To investigate this issue further, female rats with a regular 4-day estrous cycle have been injected sc 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 sc 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, FSH, and PRL. The data obtained from naloxone-treated animals were compared to those derived from controls injected sc with 0.9% saline solution and killed at the same time intervals. The sc injections of naloxone stimulated LH release in every phase of the estrous cycle; however 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. These findings suggest that, in normally cycling adult female rats, naloxone exerts a stimulatory effect on LH release during each day of the estrous cycle; that the stimulatory effect of naloxone is minimal at the time of the spontaneous proestrous LH surge; and that 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.
越来越明显的是，阿片类激动剂和拮抗剂对促性腺激素和催乳素释放的影响可能会因内分泌环境而异。为了进一步研究这个问题，对具有规律4天发情周期的雌性大鼠在发情周期的不同日子里，于一天中的不同时间皮下注射阿片类拮抗剂纳洛酮。在动情间期的第一天和第二天的1000和1600时，以及在发情前期和发情期的1000、1200、1400、1600、1800和2000时，在皮下注射纳洛酮（2.5毫克/千克溶解于0.9%盐溶液）20分钟后处死动物。通过断头法处死动物，收集躯干血并测定LH、FSH和PRL。将从纳洛酮处理的动物获得的数据与从皮下注射0.9%盐溶液并在相同时间间隔处死的对照动物获得的数据进行比较。皮下注射纳洛酮在发情周期的每个阶段都刺激LH释放；然而，反应的幅度变化很大。在动情间期的2天、发情前期的1000和1400时以及发情期的1600、1800和2000时，观察到增加幅度为700 - 1000%。在发情前期的1600时以及发情期的1000、1200和1400时观察到更高的反应（约为2700 - 3300%）。在发情前期的1800和2000时，LH对纳洛酮的反应似乎消失了。在所考虑的任何时间间隔内，治疗均未影响FSH和PRL的血清水平。这些发现表明，在正常发情周期的成年雌性大鼠中，纳洛酮在发情周期的每一天都对LH释放产生刺激作用；纳洛酮的刺激作用在自发性发情前期LH峰出现时最小；相反，纳洛酮对LH释放的作用在自发性发情前期LH峰出现前以及发情期的1400时最大。纳洛酮不影响FSH和PRL释放这一观察结果再次强调了控制LH、FSH和PRL分泌的中枢机制是不同的。
