Foresta C, Scanelli G, Tramarin A, Scandellari C
Fertil Steril. 1985 Mar;43(3):447-50. doi: 10.1016/s0015-0282(16)48447-5.
Endogenous opioid peptides exert a tonic inhibition on gonadotropin secretion at the hypothalamic level, but the mechanisms by which they act are still unknown. Previous experimental studies suggest that the endogenous opioid peptides change dopaminergic and serotoninergic tones at the hypothalamic level. We have investigated whether the stimulatory effect of naloxone on luteinizing hormone (LH) secretion is due to its influence on these neurotransmitters. Two experimental models were studied, and two sets of effects on LH secretion induced by intravenous naloxone infusion (20 mg over 2 hours) in 14 normal men 20 to 25 years of age were evaluated: the effect of oral sulpiride (150 mg), a potent dopaminergic antagonist, and the effect of oral fenfluramine (60 mg), a drug that stimulates the serotoninergic receptors by releasing serotonin and inhibiting its reuptake. The study demonstrated that naloxone infusion significantly stimulated the LH secretion throughout the period of observation (P less than 0.01 versus saline). The pretreatment with sulpiride did not change the LH response to naloxone. After fenfluramine pretreatment, naloxone failed to induce any rise in LH secretion. Follicle-stimulating hormone did not show any important variation in either test. The data suggest that in man the stimulatory ability of the opiate receptor antagonist naloxone to elicit a rise in LH plasma levels may involve the serotoninergic, but not the dopaminergic, hypothalamic system. This hypothesis, however, does not exclude the involvement of other hypothalamic neurotransmitters.
内源性阿片肽在下丘脑水平对促性腺激素分泌发挥着持续性抑制作用，但其作用机制仍不清楚。以往的实验研究表明，内源性阿片肽可改变下丘脑水平的多巴胺能和5-羟色胺能张力。我们研究了纳洛酮对促黄体生成素（LH）分泌的刺激作用是否归因于其对这些神经递质的影响。研究了两种实验模型，并评估了静脉输注纳洛酮（2小时内20毫克）对14名20至25岁正常男性LH分泌产生的两组效应：强效多巴胺能拮抗剂口服舒必利（150毫克）的效应，以及通过释放5-羟色胺并抑制其再摄取来刺激5-羟色胺能受体的药物口服芬氟拉明（60毫克）的效应。研究表明，在整个观察期内，输注纳洛酮均显著刺激LH分泌（与生理盐水相比，P<0.01）。舒必利预处理并未改变LH对纳洛酮的反应。芬氟拉明预处理后，纳洛酮未能引起LH分泌的任何升高。在两项试验中，促卵泡生成素均未显示出任何重要变化。数据表明，在人类中，阿片受体拮抗剂纳洛酮引起LH血浆水平升高的刺激能力可能涉及下丘脑5-羟色胺能系统，而非多巴胺能系统。然而，这一假说并不排除其他下丘脑神经递质的参与。
