Data for: Corticosteroid-binding globulin (SERPINA6) establishes postpubertal sex differences in rat adrenal development

<b>Abstract</b><br/><p>Encoded by SerpinA6, plasma corticosteroid-binding globulin (CBG) transports glucocorticoids and regulates their access to cells. We determined how CBG influences plasma corticosterone and adrenal development in rats during the pubertal to adult transition using CRISPR/cas9 to disrupt SerpinA6 gene expression. In the absence of CBG, total plasma corticosterone levels were ∼80% lower in adult rats of both sexes, with a greater absolute reduction in females than in males. Notably, free corticosterone and adrenocorticotropic hormone were comparable between all groups. Between 30 and 90 days of age, wild-type female rats showed increases in adrenal weight and the size of the corticosterone-producing region, the zona fasciculata (zf), in tandem with increases in plasma CBG and corticosterone concentrations, whereas no such changes were observed in males. This sex difference was lost in rats without CBG, such that adrenal growth and zf expansion were similar between sexes. The sex-specific effects of CBG on adrenal morphology were accompanied by remarkable changes in gene expression: ∼40% of the adrenal transcriptome was altered in females lacking CBG, whereas almost no effect was seen in males. Over half of the adrenal genes that normally exhibit sexually dimorphic expression after puberty were similarly expressed in males and females without CBG, including those responsible for cholesterol biosynthesis and mobilization, steroidogenesis, and growth. Rat adrenal SerpinA6 transcript levels were very low or undetectable. Thus, sex differences in adrenal growth, morphology and gene expression profiles that emerge during puberty in rats are dependent on concomitant increases in plasma CBG produced by the liver.</p>

**摘要** 血浆皮质类固醇结合球蛋白（corticosteroid-binding globulin，CBG）由丝氨酸蛋白酶抑制剂A6（SerpinA6）编码，负责转运糖皮质激素并调控其向细胞的递送。本研究借助CRISPR/Cas9技术干扰SerpinA6基因表达，探究了CBG对大鼠从青春期向成年期过渡过程中血浆皮质酮水平与肾上腺发育的影响。结果显示，在无CBG的成年雌雄大鼠体内，血浆总皮质酮水平均下降约80%，且雌性个体的绝对降幅高于雄性。值得注意的是，所有组别大鼠的游离皮质酮与促肾上腺皮质激素（adrenocorticotropic hormone）水平均无显著差异。在30至90日龄期间，野生型雌性大鼠的肾上腺重量、皮质酮合成部位肾上腺皮质束状带（zona fasciculata，简称zf）的体积随血浆CBG与皮质酮浓度升高同步增加，而雄性大鼠未出现此类变化。这种性别差异在CBG缺失的大鼠中完全消失，雌雄个体的肾上腺生长与zf扩张程度趋于一致。CBG对肾上腺形态的性别特异性影响伴随显著的基因表达改变：缺失CBG的雌性大鼠肾上腺转录组中约40%的基因表达发生改变，而雄性大鼠几乎未受影响。青春期后正常呈现性别二态性表达的肾上腺基因中，超过一半在CBG缺失的雌雄大鼠中表达模式趋于一致，其中包括参与胆固醇生物合成与动员、类固醇生成以及细胞生长的相关基因。大鼠肾上腺组织中SerpinA6的转录本水平极低甚至无法检测到。综上，大鼠青春期出现的肾上腺生长、形态及基因表达谱的性别差异，依赖于肝脏合成的血浆CBG水平的同步升高。