Background
Cortisol, also known as hydrocortisone, is a natural glucocorticoid hormone synthesized in the adrenocortical zona fasciculata using cholesterol as a precursor, and transported through the bloodstream to target cells to exert physiological effects. Glucocorticoids are found in two states in the bloodstream, a free state in which they can diffuse freely into target cells to act, and a bound state in which they are tightly bound to albumin or corticosteroid transporter globulin, which functions as a reservoir of free cortisol and ensures that cortisol is in a state of even distribution in the bloodstream. In general, total adult cortisol secretion is 15-25 mg/d, 116-185 mg/d in the perioperative period, and up to 500 mg/d when intense stress is present. Cortisol has a half-life of 70-120 min in the blood and is degraded primarily in the liver, other sites of degradation include the kidneys, connective tissues, and the adrenal glands themselves.
Cortisol can influence various aspects of physiological processes in the body through genomic and non-genomic actions. It inhibits infectious or non-infectious inflammation, promotes protein and glucose catabolism, and influences lipolysis and redistribution. It also affects immune function, increases catecholamine and angiotensin II sensitivity, and prolongs wound healing time. Cortisol has also been found to reduce capillary permeability, reduce cerebral edema, reduce sodium and water retention caused by water excretion, promote fetal tissue cell differentiation and maturation, and regulate thyroid hormones as well as inhibit sex hormones.
Figure 1. Role of cortisol in health
(Source: Zefferino R, et al. 2021)
Cortisol synthesis and secretion are mainly regulated by the hypothalamic-pituitary-adrenal (HPA) axis and are influenced by feedback, stress, cytokines, and circadian rhythms. Negative feedback regulation is the most important form of regulation, which ensures that the hormone just meets the needs of the body, while at the same time keeping the level of HPA-axis-related hormones in a relatively stable state. Stress stimulates the synthesis and secretion of adrenocorticotropic hormone (ACTH) and cortisol. Cortisol helps the body to defend itself against injurious reactions when it is in a state of stress such as fever, exercise, surgery, or low blood pressure. In addition, circadian rhythms are important factors influencing ACTH and cortisol secretion. Plasma ACTH and cortisol levels are highest in healthy adults around the time of awakening in the morning, then gradually decline, reach their lowest values during late night sleep, and then gradually rise. This circadian rhythm is associated with the day-night transition and human wakefulness patterns.
References
- 1. Zefferino R, et al. Molecular links between endocrine, nervous and immune system during chronic stress. Brain Behav. 2021 Feb;11(2):e01960.
- 2. Lightman SL, et al. Dynamics of ACTH and Cortisol Secretion and Implications for Disease. Endocr Rev. 2020 Jun 1;41(3):bnaa002.