Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, Canada.
J Endocrinol. 2021 Jan;248(1):R1-R17. doi: 10.1530/JOE-20-0286.
Normal function of the hypothalamic-pituitary-adrenal (HPA) axis is critical for survival, and its development is choreographed for age-, sex- and context-specific actions. The liver influences HPA ontogeny, integrating diverse endocrine signals that inhibit or activate its development. This review examines how developmental changes in the expression of genes in the liver coordinate postnatal changes in multiple endocrine systems that facilitate the maturation and sexual dimorphism of the rat HPA axis. Specifically, it examines how the ontogeny of testicular androgen production, somatostatin-growth hormone activities, and hypothalamic-pituitary-thyroid axis activity intersect to influence the hepatic gene expression of insulin-like growth factor 1, corticosteroid-binding globulin, thyroxine-binding globulin, 11β-hydroxysteroid dehydrogenase type 1 and 5α-reductase type 1. The timing of such molecular changes vary between mammalian species, but they are evolutionarily conserved and are poised to control homeostasis broadly, especially during adversity. Importantly, with the liver as their nexus, these diverse endocrine systems establish the fundamental organization of the HPA axis throughout postnatal development, and thereby ultimately determine the actions of glucocorticoids during adulthood.
下丘脑-垂体-肾上腺 (HPA) 轴的正常功能对生存至关重要，其发育是为年龄、性别和特定环境的作用而编排的。肝脏影响 HPA 的个体发生，整合了多种内分泌信号，抑制或激活其发育。这篇综述探讨了肝脏中基因表达的发育变化如何协调多种内分泌系统的产后变化，从而促进大鼠 HPA 轴的成熟和性别二态性。具体来说，它研究了睾丸雄激素产生、生长抑素-生长激素活性和下丘脑-垂体-甲状腺轴活性的个体发生如何相互作用，以影响胰岛素样生长因子 1、皮质类固醇结合球蛋白、甲状腺素结合球蛋白、11β-羟类固醇脱氢酶 1 和 5α-还原酶 1 的肝基因表达。这些分子变化的时间在哺乳动物物种之间有所不同，但它们在进化上是保守的，并且准备好广泛控制体内平衡，尤其是在逆境中。重要的是，通过肝脏作为它们的枢纽，这些不同的内分泌系统在整个产后发育过程中建立了 HPA 轴的基本组织，从而最终决定了成年期糖皮质激素的作用。
