Ulloa-Aguirre A, Mendez J P, Gonzalez-Castillo A, Carranza-Lira S, Garza-Flores J, Peres-Palacios G
Department of Reproductive Biology, National Institute of Nutrition S. Zubiran, Mexico City, Mexico.
Clin Endocrinol (Oxf). 1988 Jul;29(1):17-28. doi: 10.1111/j.1365-2265.1988.tb00245.x.
The present study investigated the time of male sexual maturation during which hypothalamic inhibitory opioid activity can be detected. Normal prepubertal (Tanner stage G 1 (Ts-G1) (n = 4], early pubertal (Ts-G2 (n = 5], pubertal (Ts-G3 (n = 4), and Ts-G4 (n = 2] and adult subjects (Ts-G5 (n = 4] receives a rapid infusion of the selective opiate antagonist nalocone (NAL) (20 mg over 10 min). LH secretion was assessed by frequent (every 10 min for 2 h) venous sampling before and after administration of the opiate blocker, as well as by the LH response to exogenous GnRH. All but one (a Ts-G2 subject) pubertal boys showed aprompt and sustained increase in serum LH concentrations after NAL administration, as disclosed by the areas under the LH curve (aLHc) calculated from samples obtained before and after NAL infusion (aLHc in four Ts-G2 responders, 162 +/- 20 (mean +/- SEM) vs 314 +/- 56 mIU/ml/min before and after NAL respectively, P less than 0.025; Ts-G3, 227 +/- 35 vs 362 +/- 56 mIU/ml/min, P less than 0.025; Ts-G4 and Ts-G5, 432 +/- 77 vs 687 +/- 91 mIU/ml/min, P less than 0.05). In contrast, none of the prepubertal children had significant changes in LH secretion after the NAL challenge (154 +/- 17 vs 154 +/- 9 mIU/ml/min). Although all NAL responders exhibited serum testosterone (T) levels above 5 nmol/l, a positive correlation between individual T values and magnitude of LH responses to NAL was not found. All subjects had significant serum LH increments after GnRH administration. In a second series of studies, additional groups of Ts-G1 subjects were primed during 5 days either with GnRH alone or with GnRH plus sex steroids (ethinyl oestradiol 12.5 micrograms/12 h or testosterone enanthate 1.8 mg/kg body weight (single dose], before NAL administration, to investigate whether hypothalamic opioid activity might be unmasked by additional sex steroids. None of the priming schemes significantly modified the pituitary LH responses to NAL infusion (GnRH-primed group, 145 +/- 48 vs 139 +/- 43 mIU/ml/min before and after NAL, respectively; GnRH plus ethinyl oestradiol-primed group, 124 +/- 42 vs 107 +/- 34 mIU/ml/min; GnRH plus testosterone enanthate-primed group, 64 +/- 10 vs 57 +/- 24 mIU/ml/min). This study suggests that the development and/or maturation of the opioid control of LH secretion is temporally related with the onset of puberty.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究调查了能够检测到下丘脑抑制性阿片样物质活性的男性性成熟时间。正常青春期前（坦纳分期G1期（Ts-G1）（n = 4））、青春期早期（Ts-G2期（n = 5））、青春期（Ts-G3期（n = 4））、Ts-G4期（n = 2）以及成年受试者（Ts-G5期（n = 4））接受快速输注选择性阿片拮抗剂纳洛酮（NAL）（10分钟内输注20毫克）。在给予阿片阻滞剂之前和之后，通过频繁（每10分钟一次，共2小时）静脉采血评估促黄体生成素（LH）分泌，以及通过LH对外源性促性腺激素释放激素（GnRH）的反应进行评估。除一名（一名Ts-G2期受试者）青春期男孩外，所有青春期男孩在给予NAL后血清LH浓度均迅速且持续升高，这通过计算NAL输注前后样本的LH曲线下面积（aLHc）得以揭示（四名Ts-G2期反应者的aLHc，分别为162±20（平均值±标准误）与NAL给药前后的314±56毫国际单位/毫升/分钟，P<0.025；Ts-G3期，227±35与362±56毫国际单位/毫升/分钟，P<0.025；Ts-G4期和Ts-G5期，432±77与687±91毫国际单位/毫升/分钟，P<0.05）。相比之下，青春期前儿童在接受NAL激发后LH分泌无显著变化（154±17与154±9毫国际单位/毫升/分钟）。尽管所有NAL反应者的血清睾酮（T）水平均高于5纳摩尔/升，但未发现个体T值与LH对NAL反应幅度之间存在正相关。所有受试者在给予GnRH后血清LH均有显著升高。在第二项系列研究中，在给予NAL之前，额外的Ts-G1期受试者组分别在5天内单独用GnRH或用GnRH加性类固醇（炔雌醇12.5微克/12小时或庚酸睾酮1.8毫克/千克体重（单次剂量））进行预处理，以研究额外的性类固醇是否可能揭示下丘脑阿片样物质活性。没有一种预处理方案能显著改变垂体对NAL输注的LH反应（GnRH预处理组，分别为145±48与NAL给药前后的139±43毫国际单位/毫升/分钟；GnRH加炔雌醇预处理组，124±42与107±34毫国际单位/毫升/分钟；GnRH加庚酸睾酮预处理组，64±10与57±24毫国际单位/毫升/分钟）。本研究表明，LH分泌的阿片样物质控制的发育和/或成熟在时间上与青春期的开始相关。（摘要截短至400字）
