INSERM U 669, Troubles des Conduites Alimentaires à l'Adolescence, Paris, France.
PLoS One. 2011 Mar 8;6(3):e16704. doi: 10.1371/journal.pone.0016704.
Several studies in animal models suggest a possible effect of the specific part of the Y-chromosome (Y(NPAR)) on brain opioid, and more specifically on brain β-endorphin (BE). In humans, male prevalence is found in autistic disorder in which observation of abnormal peripheral or central BE levels are also reported. This suggests gender differences in BE associated with genetic factors and more precisely with Y(NPAR).
METHODOLOGY/PRINCIPAL FINDINGS: Brain BE levels and plasma testosterone concentrations were measured in two highly inbred strains of mice, NZB/BlNJ (N) and CBA/HGnc (H), and their consomic strains for the Y(NPAR). An indirect effect of the Y(NPAR) on brain BE level via plasma testosterone was also tested by studying the correlation between brain BE concentration and plasma testosterone concentration in eleven highly inbred strains. There was a significant and major effect (P<0.0001) of the Y(NPAR) in interaction with the genetic background on brain BE levels. Effect size calculated using Cohen's procedure was large (56% of the total variance). The variations of BE levels were not correlated with plasma testosterone which was also dependent of the Y(NPAR).
CONCLUSIONS/SIGNIFICANCE: The contribution of Y(NPAR) on brain BE concentration in interaction with the genetic background is the first demonstration of Y-chromosome mediated control of brain opioid. Given that none of the genes encompassed by the Y(NPAR) encodes for BE or its precursor, our results suggest a contribution of the sex-determining region (Sry, carried by Y(NPAR)) to brain BE concentration. Indeed, the transcription of the Melanocortin 2 receptor gene (Mc2R gene, identified as the proopiomelanocortin receptor gene) depends on the presence of Sry and BE is derived directly from proopiomelanocortin. The results shed light on the sex dependent differences in brain functioning and the role of Sry in the BE system might be related to the higher frequency of autistic disorder in males.
几项动物模型研究表明，Y 染色体的特定部分（Y（NPAR））可能对大脑阿片类物质产生影响，更具体地说是对大脑β-内啡肽（BE）产生影响。在人类中，自闭症中发现了男性患病率，在自闭症中也观察到了外周或中枢 BE 水平异常的报道。这表明 BE 与遗传因素存在性别差异，更确切地说是与 Y（NPAR）有关。
方法/主要发现：在两个高度近交的小鼠品系，NZB/BlNJ（N）和 CBA/HGnc（H）及其 Y（NPAR）的同源品系中，测量了大脑 BE 水平和血浆睾酮浓度。还通过研究 11 个高度近交品系中大脑 BE 浓度与血浆睾酮浓度之间的相关性，测试了 Y（NPAR）通过血浆睾酮对大脑 BE 水平的间接影响。Y（NPAR）与遗传背景的相互作用对大脑 BE 水平有显著的主要影响（P<0.0001）。使用 Cohen 程序计算的效应大小很大（总方差的 56%）。BE 水平的变化与血浆睾酮不相关，而血浆睾酮也依赖于 Y（NPAR）。
结论/意义：Y（NPAR）与遗传背景相互作用对大脑 BE 浓度的贡献是 Y 染色体对大脑阿片类物质控制的首次证明。由于 Y（NPAR）所包含的基因都不编码 BE 或其前体，我们的结果表明性别决定区（Sry，由 Y（NPAR）携带）对大脑 BE 浓度有贡献。事实上，黑素皮质素 2 受体基因（Mc2R 基因，被鉴定为前阿黑皮素原受体基因）的转录依赖于 Sry 的存在，而 BE 直接来源于前阿黑皮素原。这些结果揭示了大脑功能的性别差异，Sry 在 BE 系统中的作用可能与男性自闭症发病率较高有关。
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