There are several critical developmental stages must be attained to ensure proper functionality of the HPA axis and appropriate behavioral and physiological stress-responses in adulthood. The HPA axis consists of a cascade of endocrine pathways that respond to specific negative feedback loops involving the hypothalamus, anterior pituitary gland, and adrenal gland. A major component of the homeostatic response is the hypothalamic-pituitary-adrenal (HPA) axis, an intricate, yet robust, neuroendocrine mechanism that mediates the effects of stressors by regulating numerous physiological processes, such as metabolism, immune responses, and the autonomic nervous system (ANS). Humans and animals respond to environmental perturbations with a stress response that allows physiological adaptation to the stressor to maintain homeostasis. We will also examine the maternal-fetal hypothalamic-pituitary-adrenal axis and disruption of the normal fetal environment which becomes a major risk factor for many neurodevelopmental pathologies in adulthood, such as major depressive disorder, anxiety, schizophrenia, and others.

In this review, we will discuss the regulation of the HPA axis and its development. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis.

2Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States.

1Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.

Hormones of adrenal