Cortisol

Cortisol, or hydrocortisone, is a steroid hormone produced by the outer layer of the adrenal glands sitting on top of each kidney. Steroid hormones, such as progesterone and testosterone, contain four fused rings of together 17 carbon atoms with varying functional groups. Cortisol, also known as the stress hormone, is a metabolic hormone regulating the body’s stress response (fight or flight), the sleep-wake cycle, and the metabolism of muscles, fat, liver, and bones.

Research has found that cortisol affects almost every organ by regulating metabolism and suppressing inflammation. Chronically high cortisol levels can cause Cushing’s syndrome, while too little cortisol can cause Addison’s disease. However, there are a variety of other ways that either acute or chronic abnormal cortisol levels can impact human health.

Cortisol and sleep

As part of the hypothalamic-pituitary-adrenal axis, the adrenal glands produce and release cortisol following a diurnal rhythm: Levels of cortisol are high in the morning, peaking when waking up. In the following hours, cortisol levels drop rapidly and then more slowly, reaching a low around midnight¹. Accordingly, cortisol synchronizes the timing of the peripheral clocks in liver, muscle, and adipose tissue releasing energy from stored glycogen, protein, and fat. Since cortisol further affects metabolically relevant organs such as the pancreas and gut, it is the key signal for metabolic synchronization.

The plasma cortisol level is impacted by sleep hygiene, sleep disruption, and sleep duration. Sleep restrictions or accumulated sleep debt over time lead to altered cortisol production, resulting in changes in cortisol signaling. Such a disruptions mainly impact the insulin metabolism and blood glucose levels thus inducing pre-diabetes, type 2 diabetes mellitus, diabetic complications, and obesity².

Cortisol and stress

When the body experiences stress, the adrenal glands release cortisol. A corticosteroid binding globulin transports cortisol in the blood stream, which can be measured as blood cortisol, urinary cortisol, or salivary cortisol. Only up to 5% of the circulating cortisol is unbound and thus free cortisol. Upon binding to glucocorticoid receptors and diffusing into liver, muscle, or adipose tissue, cortisol regulates their metabolisms by quickly releasing metabolic substrates such as glucose, raising blood sugar levels.

As such, cortisol levels are impacted by acute stresses such as exercise and by chronic stresses such as loneliness and other emotional states. For example, patients with lower cortisol peaks in the morning show clinical symptoms of depression. On the contrary, during short-term stress periods, cortisol signaling provides energy to the body to fuel the fight or flight response, which favors the sympathetic nervous system over the parasympathetic nervous system.

However, constant stress with high cortisol levels over longer time periods induces the production and storage of lipids triggering weight gain and impacting cardiovascular health³. To counteract these effects, stress-alleviating therapies, like massages, good sleep hygiene, and mindfulness approaches were shown to control cortisol levels and thus the body’s stress reactions.

Cortisol and exercise

As part of the body’s stress response system, cortisol levels significantly impact exercise sessions, muscle recovery, and adaptation to long-term physical training⁴. During exercise, cortisol triggers the release of metabolic substrates to provide energy, protects against muscle inflammation, and strengthens blood vessels.

For about two hours after exercise, cortisol levels remain high with increased tissue sensitivity to glucocorticoids to counteract the inflammatory response and prevent muscle damage⁵. Furthermore, tissues and muscles adapt to exercise training as athletes display both higher cortisol and testosterone levels along with lower inactivation rates of cortisol.

Cortisol and cardiovascular disease

As outlined above, cortisol plays a key role in metabolic pathways to provide energy to different tissues. Additionally, cortisol has a direct impact on the heart, blood vessels, and cardiometabolic markers including diabetes and adiposity. Since the metabolism of both cortisol and bile acids are tightly linked, cortisol can cause the development of health problems related to weight gain, such as liver diseases and high blood pressure⁶.

The increased cortisol synthesis over longer time periods leads to the delivery and storage of cortisol in hair capillaries. A growing body of research suggests a link between increased hair cortisol concentrations and cardiovascular symptoms like high blood pressure, diabetes, and weight gain⁷. While the underlying mechanisms of this hormonal regulation are still unclear, the levels of cortisol inside of hair are a promising biomarker of both chronic stress and cardiovascular diseases⁸.

Metabolon’s Biological Stress Discovery Panel

Metabolon’s Biological Stress Discovery Panel measures 114 key biological stress metabolites, including cortisol. Metabolon has created a suite of tools built from decades of experience across thousands of metabolomics studies to help you understand the crucial role of steroid hormones and their derivatives in disorders and pathways. Contact us today to learn more about our Biological Stress Discovery Panel and how Metabolon can help you advance your research.

References

1. De Nys L, Anderson K, Ofosu EF et al. The effects of physical activity on cortisol and sleep: A systematic review and meta-analysis. Psychoneuroendocrinology 2022;143:105843.
2. Liu PY and Reddy RT. Sleep, testosterone and cortisol balance, and ageing men. Rev Endocr Metab Disord 2022;23(6):1323–1339.
3. Linderborg KM, Kortesniemi M, Aatsinki AK et al. Interactions between cortisol and lipids in human milk. Int Breastfeed J 2020;15(1):66.
4. Kraemer WJ, Ratamess NA, Hymer WC et al. Growth Hormone(s), Testosterone, Insulin-Like Growth Factors, and Cortisol: Roles and Integration for Cellular Development and Growth With Exercise. Front Endocrinol (Lausanne) 2020;11:33.
5. Gouarné C, Groussard C, Gratas-Delemarche A et al. Overnight Urinary Cortisol and Cortisone Add New Insights into Adaptation to Training. Med Sci Sports Exerc 2005;37(7):1157–1167.
6. Nowotny H, Ahmed SF, Bensing S et al. Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis. Endocrine 2021;71(3):586–594.
7. Adam EK, Quinn ME, Tavernier R et al. Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology 2017;83:25–41.
8. Job E and Steptoe A. Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress. Curr Cardiol Rep 2019;21(10):116.