α-促黑素细胞激素（α-MSH）与阿片类物质在调节人类促性腺激素分泌过程中存在相互作用的证据。
Evidence for an interaction between alpha-MSH and opioids in the regulation of gonadotropin secretion in man.
作者信息
Limone P, Calvelli P, Altare F, Ajmone-Catt P, Lima T, Molinatti G M
机构信息
Department of Internal Medicine, Regina Margherita Hospital, Torino, Italy.
出版信息
J Endocrinol Invest. 1997 Apr;20(4):207-10. doi: 10.1007/BF03346904.
Gonadotropin secretion is inhibited by the endogenous opioids and stimulated by their antagonist naloxone. LH secretion is stimulated by alpha-MSH, a tridecapeptide derived from the post-translational processing of POMC. The possibility that alpha-MSH interacts with the opioids, as suggested by the experimental evidence, was investigated in 7 normal males aged 24-29 through the performance of seven tests: naloxone (0.8 mg i.v. bolus, followed by infusion of 1.6 mg/h for 120'); alpha-MSH (2.5 mg i.v. bolus); naloxone + alpha-MSH (2.5 mg i.v. 15' after commencement of the naloxone infusion); naloxone + GnRH (100 micrograms i.v. 15' after commencement of the naloxone infusion); alpha-MSH + GnRH (respectively 2.5 mg and 100 micrograms at time 0), GnRH alone (100 micrograms at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3 +/- 2.7 mIU/ml.min-1) and alpha-MSH test (32.9 +/- 4.6 mIU/ml.min-1) were significantly greater (p < 0.005) than that observed during placebo (16.9 +/- 3.6 mIU/ml.min-1). The LH AUC during alpha-MSH + naloxone (37.6 +/- 2.6 mIU/ml.min-1) was not significantly different from that recorded during their separate administration. GnRH injected alone, during the naloxone infusion and with alpha-MSH produced similar increases in LH, that were significantly higher than that observed during the other tests (AUCs: GnRH 89.4 +/- 10.6, GnRH + naloxone 100.5 +/- 9.1, GnRH + alpha-MSH 94.6 +/- 7.9 mIU/ml.min-1, p < 0.001). Significant increase in FSH (p < 0.001) was only observed during GnRH, GnRH + naloxone and GnRH + aMSH tests (AUCs: placebo 13.3 +/- 1.7; naloxone 14.7 +/- 2.5; alpha-MSH 15.5 +/- 2.3; alpha-MSH + naloxone 16.9 +/- 1.9; GnRH 19.1 +/- 1.1; GnRH + alpha-MSH 20.7 +/- 1.3; GnRH + naloxone 21.2 +/- 1.8 mIU/ml.min-1). These results are in line with the possibility of an interaction between alpha-MSH and the opioids in the regulation of gonadotropin secretion, perhaps with opposing effects on a final common pathway.
促性腺激素的分泌受内源性阿片类物质抑制，而受其拮抗剂纳洛酮刺激。促黄体生成素（LH）的分泌受α-促黑素细胞激素（α-MSH）刺激，α-MSH是一种由阿片-促黑素细胞皮质素原（POMC）翻译后加工产生的十三肽。根据实验证据所提示的α-MSH与阿片类物质相互作用的可能性，对7名年龄在24至29岁的正常男性进行了七项试验加以研究：纳洛酮（静脉推注0.8mg，随后以1.6mg/h的速度输注120分钟）；α-MSH（静脉推注2.5mg）；纳洛酮+α-MSH（在纳洛酮输注开始15分钟后静脉注射2.5mg）；纳洛酮+促性腺激素释放激素（GnRH，在纳洛酮输注开始15分钟后静脉注射100μg）；α-MSH+GnRH（分别在0时刻注射2.5mg和100μg），单独注射GnRH（在0时刻注射100μg），安慰剂（150nmol/L氯化钠溶液）。在纳洛酮试验（30.3±2.7mIU/ml·min⁻¹）和α-MSH试验（32.9±4.6mIU/ml·min⁻¹）期间，LH的曲线下面积（AUC）均显著大于安慰剂试验期间观察到的数值（16.9±3.6mIU/ml·min⁻¹，p<0.005）。α-MSH+纳洛酮试验期间的LH AUC（37.6±2.6mIU/ml·min⁻¹）与单独给药时记录的数值无显著差异。单独注射GnRH、在纳洛酮输注期间注射GnRH以及与α-MSH联合注射GnRH均使LH产生类似的升高，且显著高于其他试验所观察到的数值（AUC：GnRH为89.4±10.6、GnRH+纳洛酮为100.5±9.1、GnRH+α-MSH为94.6±7.9mIU/ml·min⁻¹，p<0.001）。仅在GnRH、GnRH+纳洛酮和GnRH+α-MSH试验期间观察到促卵泡生成素（FSH）有显著升高（p<0.001）（AUC：安慰剂为13.3±1.7；纳洛酮为14.7±2.5；α-MSH为15.5±2.3；α-MSH+纳洛酮为16.9±1.9；GnRH为19.1±1.1；GnRH+α-MSH为20.7±1.3；GnRH+纳洛酮为21.2±1.8mIU/ml·min⁻¹）。这些结果符合α-MSH与阿片类物质在调节促性腺激素分泌过程中相互作用的可能性，可能对最终的共同途径产生相反的影响。
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