Liver at the nexus of rat postnatal HPA axis maturation and sexual dimorphism

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, 11 beta-hydroxysteroid dehydrogenase type 1 and 5 alpha-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.

Automated summary

The normal function of the HPA axis is crucial for survival, and liver gene expression plays a key role in orchestrating its development by integrating various endocrine signals. Developmental changes in different endocrine systems during infancy influence the maturation and sexual dimorphism of the HPA axis, ultimately determining the actions of glucocorticoids during adulthood.