Neurobiology for the sex differences in energy balance

体重平衡中存在性别二形性，但潜在的机制仍然难以捉摸。我们 筛选了一些已知在能量调节中起关键作用的神经种群 动态平衡，并发现表达前阿片黑素皮质素(POMC)的下丘脑神经元表现出性别 在两个基本功能上的差异：(1)表达POMC基因和(2)放电动作电位。在……里面 特别是，雌性POMC神经元比雄性POMC神经元表达更多的POMC基因和更频繁的放电 神经元。这种性别二型性的机制尚不清楚，也几乎不知道这些性别 不同的性别对能量平衡的调节是不同的。通过POMC神经元特异性 通过转录组分析，我们确定了一些以性别二态方式表达的基因。 其中包括TAp63(一种在雌性POMC神经元中占主导地位的转录因子)，以及Gabra5 (GABAA受体亚单位)和SK3(小电导钙激活的K+通道)都是 在雄性POMC神经元中占优势。将产生三只分别具有这三种基因的突变小鼠 分别在POMC神经元中特异性缺失。这些老鼠品系(包括雄性和雌性)将是 用于确定这三个基因在调节POMC神经元放电和/或POMC中的生理作用 基因表达，以及维持不同性别的能量动态平衡。功能相互作用 这些性二态基因与性激素之间的关系也将得到检验。来自这些的结果 研究将检验一种假设，即POMC神经元中的多种性二态基因有助于 POMC神经元功能和体重平衡的性别差异。

Sexual dimorphism exists in body weight balance, but underlying mechanisms remain elusive. We screened a number of neural populations that are known to play key roles in the regulation of energy homeostasis, and found that hypothalamic neurons expressing pro-opiomelanocortin (POMC) display sex differences in two fundamental functions: (1) expressing the Pomc gene and (2) firing action potentials. In particular, female POMC neurons express more Pomc gene and firing more frequently than male POMC neurons. Mechanisms for this sexual dimorphism are not clear and little is known about whether these sex differences contribute to sexually dimorphic regulation of energy balance. Through POMC neuron-specific transcriptome analyses, we identified a number of genes that are expressed in a sexually dimorphic fashion. These include TAp63 (a transcription factor) which is dominant in female POMC neurons, as well as Gabra5 (a GABAA receptor subunit) and SK3 (a small-conductance Ca2+-activated K+ channel) which are both dominant in male POMC neurons. Three mutant mice will be generated to have each of these three genes deleted specifically in POMC neurons, respectively. These mouse strains (both males and females) will be used to determine the physiological roles of these three genes in regulating POMC neuron firing and/or Pomc gene expression, and in maintaining energy homeostasis in different sexes. The functional interactions between these sexually dimorphic genes with the sex hormones will also be examined. Results from these studies will test a hypothesis that multiple sexually dimorphic genes in POMC neurons contribute to the sex differences in POMC neuron functions and body weight balance.