阿片受体μ对睾丸间质细胞影响的外周机制研究

The effects of opioids on Leydig cells are involved in peripheral mechanisms of Opioid-Induced Androgen Deficiency (OPIAD), but the pathway from opioid receptor mu to Leydig cells is unclear. The results of preliminary experiments conducted by our team revealed that the agonist of opioid receptor mu DAMGO specifically inhibited secretion of IGF-1 from Sertoli cells and that testosterone biosynthesis was reduced in IGF-1 null mice. Therefore, we hypothesize that IGF-1 secreted by Sertoli cells mediated by opioid receptor mu indirectly affects Leydig cells, leading to the alteration of testosterone production because of inhibition of testosterone biosynthetic enzymes. IGF-1 produced by Sertoli cells can control the physiological activities of Sertoli cells via self-feedback. The techniques of conditional knockout, knockdown of siRNA and cell co-culture will be applied to clarify the mechanisms of crosstalk between somatic cells and self-feedback of Sertoli cells in vivo, ex vivo and in vitro. The mechanism of OPIAD modulated by the pathway of opioid receptor mu /IGF-1 will be of practical significance, which can provide the theoretical basis for locally peripheral therapy of OPIAD.

阿片相关雄激素缺乏症(OPIAD)的外周机制涉及阿片对Leydig细胞的作用，但阿片受体μ对Leydig细胞的作用通路不清。我们项目组的前期实验发现阿片受体μ特异性激动剂DAMGO抑制Sertoli细胞分泌IGF-1,IGF-1敲除小鼠睾丸酮合成减少。提出假说：阿片受体μ通过Sertoli细胞分泌IGF-1，间接作用于Leydig细胞，影响睾丸酮合成酶导致睾丸酮产量改变。且Sertoli细胞分泌的IGF-1有自身反馈作用。利用条件性基因敲除，RNA干扰，非接触性细胞共培养等技术，从在体，在体-离体和体外三个层次阐明阿片受体μ/IGF-1介导的Sertoli细胞对Leydig细胞影响及Sertoli细胞自身反馈机制，为OPIAD的外周局部治疗奠定理论基础,具有现实意义。

阿片相关雄激素缺乏症(OPIAD)的外周机制涉及阿片对Leydig细胞的作用，但阿片受体μ对Leydig细胞的作用通路不清。我们项目组的前期实验发现阿片受体μ特异性激动剂DAMGO抑制Sertoli细胞分泌IGF-1,IGF-1敲除小鼠睾丸酮合成减少。提出假说：阿片受体μ通过Sertoli细胞分泌IGF-1，间接作用于Leydig细胞，影响睾丸酮合成酶导致睾丸酮产量改变。且Sertoli细胞分泌的IGF-1有自身反馈作用。利用条件性基因敲除，RNA干扰，非接触性细胞共培养等技术，从在体，在体-离体和体外三个层次阐明阿片受体μ/IGF-1介导的Sertoli细胞对Leydig细胞影响及Sertoli细胞自身反馈机制，为OPIAD的外周局部治疗奠定理论基础,具有现实意义。