Regulation of the Hypothalamic-Pituitary-Adrenal Axis

Abstract

Glucocorticoids (GCs) are essential for the maintenance of homeostasis and enable the organism to prepare for, respond to and manage stress, either physical or emotional. Cortisol, the principal GC in humans, is synthesized in the adrenal cortex. It is released in the circulation in a pulsatile and circadian pattern. GC secretion is governed by hypothalamus and pituitary. The hypothalamus senses changes in the external and internal environment that may disrupt the homeostatic balance of the organism (i.e. stressors), and responds by releasing corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from parvocellular neurons projecting from the paraventricular nucleus to the median eminence. These neurohormones are released into the anterior pituitary where they act synergistically via specific receptors (CRH-R1 and V1B receptor, respectively) to trigger the release of the adrenocorticotropic hormone (ACTH) from the corticotrope cells into the systemic circulation. In turn, ACTH exerts its actions on the adrenal cortex via specific receptors, type 2 melanocortin receptors (MC2-R), to initiate the synthesis of cortisol, which is released immediately into the systemic circulation by diffusion. Hypothalamic CRH and AVP, pituitary ACTH and adrenal GCs comprise the hypothalamic-pituitary-adrenal (HPA) axis. In this brief review, the HPA axis and the various factors that regulate its function are described.

A short‐term extremely low frequency electromagnetic field exposure increases circulating leukocyte numbers and affects HPA‐axis signaling in mice

“…Therefore, we determined upstream regulation of the HPA axis as represented by the expression of CRH in the PVN, POMC in the pituitary, and CYp11a1 in the adrenal cortex. We focused on expression of these genes since they are key in the regulation of stress hormone synthesis [Papadimitriou and Priftis, 2009], and changes at this level in the stress pathway will alter stress hormone synthesis. In our experiments no significant changes were found in the expression of CRH in the PVN and Cyp11a1 in the adrenal.…”

“…A decrease in POMC expression and ACTH levels might therefore be the result of a feedback mechanism reacting on high levels of corticosterone or activation in the adrenal. These signals may feedback on different levels in the HPA axis [Papadimitriou and Priftis, 2009]. This implies that ELF‐EMF exposure induces changes in HPA signaling.…”

Intestinal steroidogenesis

“…In the adrenal, the regulation of cortisol production is well char acterized and is the result of a complex interaction between three endocrine glands (hypothalamus, pituitary, and adrenal; HPA), which constitute the HPA axis [34]. Hypothalamic hormones (corticotropin releasing hormone and vasopressin) induce peptidic adrenocorticotropic hormone (ACTH) secretion in the anterior pituitary, which regulates the synthesis and release of cortisol from the adrenal cortex [34].…”

Identification of SPRED2 (Sprouty-related Protein with EVH1 Domain 2) as a Negative Regulator of the Hypothalamic-Pituitary-Adrenal Axis

“…CRH-induced ACTH release regulates the secretion of various hormones of the adrenal gland cortex (e.g. the mineralocorticoid aldosterone, glucocorticoids like cortisol and corticosterone, and androgens) (4,5). The stress hormones cortisol and corticosterone, respectively, act as important negative feedback regulators of the HPA axis by exerting a long feedback loop to the hypothalamus and a short loop to the pituitary.…”

“…The stress hormones cortisol and corticosterone, respectively, act as important negative feedback regulators of the HPA axis by exerting a long feedback loop to the hypothalamus and a short loop to the pituitary. CRH inhibition by ACTH also represents a short negative feedback loop (4,6). Dysregulation of the HPA axis plays a fundamental role in stress-associated pathologies, mood, neurodegenerative disorders, and anxiety (7,8).…”