Cortisol

On Cortisol
You may have heard of cortisol from people talking about stress management, or maybe you heard it in the context of weight loss. What is cortisol? How was it discovered? Why is it important? This blog serves to spread information on the hormone cortisol.

The Discovery of Cortisol

In the mid-19th century, British physician Thomas Addison observed a distinct pattern among patients suffering from severe adrenal disease: they developed fatigue, weight loss, low blood pressure, skin hyperpigmentation, and ultimately died. From these clinical observations, Addison concluded that the adrenal glands must secrete a substance essential for life. This condition, caused by adrenal insufficiency, became known as Addison’s disease, although the specific missing factor remained unknown for decades.

In the early 20th century, further research revealed that the adrenal gland consists of two functionally distinct regions, the medulla and the cortex, and that the cortex was critical not only for responding to physiological stress but for maintaining basic metabolic and circulatory stability. In the 1930s, independent research efforts led to the isolation of a steroid compound known as Compound E, which was later identified as cortisol. This hormone was found to be essential for energy mobilization, regulation of blood glucose, maintenance of vascular tone, and control of inflammation, providing the long-sought explanation for Addison’s disease.

Cortisol versus Cortisone

You may have gone to a doctor and been prescribed a cortisone injection for an injury. Cortisone is an inactive precursor of cortisol that can be converted into cortisol within tissues, allowing it to exert strong anti-inflammatory effects. When administered locally, corticosteroid injections reduce inflammation while limiting widespread exposure throughout the body.

So why don’t we simply inject cortisol directly? Cortisol acts on many tissues and regulates numerous processes, including metabolism, immune activity, vascular tone, and stress responses. Direct administration can therefore produce broad systemic effects, increasing the risk of side effects. Instead, clinicians use synthetic corticosteroids that are engineered to have more predictable durations of action, greater tissue specificity, and improved control over how they are metabolized. This approach maximizes anti-inflammatory benefits while minimizing unwanted effects elsewhere in the body.

Why is Cortisol Important?

Cortisol belongs to a family of hormones known as steroid hormones, which are all derived from cholesterol and share a characteristic four-ring (gonane) structure. Steroid hormones play essential roles in maintaining homeostasis, helping regulate metabolism, fluid balance, reproduction, and stress responses. Cortisol in particular is critical for energy metabolism, immune regulation, blood pressure maintenance, and the sleep-wake cycle, and it plays a central role in the body’s response to long-term stress.

Under conditions of chronic stress, cortisol regulation can become dysregulated, not because the adrenal glands become “fatigued,” but because the hypothalamic–pituitary–adrenal (HPA) axis alters how cortisol is released over time. Prolonged cortisol imbalance can disrupt other hormonal systems and has been associated with symptoms such as anxiety, sleep disturbances, weight changes, and impaired concentration. Conversely, insufficient cortisol signaling can lead to fatigue, brain fog, low motivation, and, in some cases, depressive symptoms.

How Does Cortisol Work?

Cortisol is secreted into the bloodstream by the adrenal cortex and travels to target tissues throughout the body. Because cortisol is a steroid hormone, it can cross cell membranes and bind to intracellular glucocorticoid receptors. Once activated, the cortisol-receptor complex moves into the nucleus, where it directly regulates gene expression by turning specific genes on or off. These genomic effects lead to changes in metabolism, immune activity, vascular tone, and stress adaptation. Because cortisol acts by altering gene transcription, its effects develop more slowly than those of hormones like adrenaline, but they are longer-lasting. Cortisol is therefore a central regulator of homeostasis and is essential for normal physiological function and survival.

On the cover: the structure of cortisol.