Sequencing of murine corticotrophs from male and female POMC-GFP mice.

Stress-related illness represents a major burden on health and society. Understanding the molecular mechanisms underlying stress responses is an important step to understand these diseases, and design treatments. Sexual dimorphism in stress responses have been extensively reported, with depression and most anxiety disorders being more prevalent in women. Corticotrophs of the anterior pituitary play a central role in the generation of hormonal stress responses, by secreting the stress hormone ACTH in response to stressful stimuli. However, their role in contributing to sexually dimorphic responses of the HPA axis is very poorly understood. We performed bulk RNA-sequencing of FACS-sorted corticotrophs from male and female POMC-GFP mice to determine the molecular determinants of sexual dimorphic traits in the activity of these cells, revealing extensive differential gene expression at the transcriptional level. This includes more than 71 mRNAs encoding ion channel subunits, which could be involved in the generation of the sexual dimorphism in their electrical activity.应激相关疾病对人类健康与社会造成了沉重负担。解析应激反应的分子机制，是理解此类疾病并研发治疗方案的重要前提。应激反应中的性别二态性已被广泛报道，抑郁症与多数焦虑障碍在女性群体中的患病率更高。垂体前叶的促肾上腺皮质激素细胞（corticotrophs）通过分泌应激激素促肾上腺皮质激素（adrenocorticotropic hormone, ACTH）响应应激刺激，在激素性应激反应的产生过程中发挥核心作用。然而，此类细胞在介导下丘脑-垂体-肾上腺（Hypothalamic-Pituitary-Adrenal, HPA）轴的性别二态性反应中的作用，目前仍未得到充分阐明。本研究对来自雄性与雌性阿黑皮素原-绿色荧光蛋白（POMC-GFP）小鼠的荧光激活细胞分选（Fluorescence-Activated Cell Sorting, FACS）纯化的促肾上腺皮质激素细胞开展批量RNA测序（bulk RNA-sequencing），以解析此类细胞活性中性别二态性特征的分子决定因素，结果揭示了转录层面广泛存在的差异基因表达现象，其中包含71余种编码离子通道亚基的mRNA，此类亚基可能参与调控此类细胞电活动的性别二态性形成过程。