Cortisol

Classification

Cortisol is produced and secreted by the adrenal glands, which consist of two parts: the adrenal cortex and the adrenal medulla. The adrenal medulla secretes catecholamines, epinephrine and norepinephrine, and the adrenal cortex secretes cortisol together with other hormones. The cortex itself consists of three parts: zona glomerulosa, zona fasciculata, and zona reticularis and each secretes a different hormone. Cortisol is secreted by zona fasciculata. It is classified as a glucocorticoid. Glucocorticoids are hormones that increase glucose concentration in blood which is one of cortisol's effects.

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As we said, cortisol stimulates gluconeogenesis - the synthesis of glucose - by doing two things. The first one is that it stimulates the liver to create more glucose. The second one is that it decreases the synthesis of new proteins and at the same increases protein catabolism, the breakdown of proteins. By doing so, it provides more amino acids to the liver for gluconeogenesis.

Cortisol also mobilizes fatty acids from adipose tissue so that they are then available in plasma as a source of energy for cells instead of glucose during starvation or stress. It also decreases glucose utilization by tissues - in other words, tissues don’t use that much glucose as a source of energy. All of this leads to increased levels of glucose which stimulates the secretion of insulin - this is the so-called diabetogenic effect. To understand the term, imagine someone who has an actual diabetes. They are, in a way, in a similar situation: they have a high concentration of glucose, which requires more insulin, which they don’t have, or the tissue is resistant to it. Cortisol creates something similar: the high glucose concentration and the need for more insulin. That's why its effect is called diabetogenic.

To summarize, gluconeogenesis is very important because it means that the body is able to mobilize glucose between meals or even during fasting and that’s essential for survival.

Cortisol also has an anti-inflammatory effect, and it can suppress the immune system. How does that happen? Cortisol decreases the formation of prostaglandins and leukotrienes, which are inflammatory mediators. Because of that, there's a decreased white blood cells mobility, which means that not that many leukocytes  get to the inflamed area and there’s then not going to be that much phagocytosis of the damaged cells. This is going to reduce the inflammation and that’s why cortisol is often used in medicine to reduce inflammations.

Cortisol also decreases the reproduction of lymphocytes, especially T lymphocytes which suppresses the immune system, and this effect is also used in medicine because you can give cortisol to patients with transplanted organs so that their bodies don’t reject them.

Cortisol also plays a role in regulating blood pressure because it up-regulates alpha₁-adrenergic receptors in arterioles. Up-regulation simply means that there’s more of the receptors. Alpha₁-adrenergic receptors are important for catecholamines – epinephrine and norepinephrine – that cause vasoconstriction.

What’s more, cortisol inhibits bone formation by inhibiting the formation of osteoblasts. This is important, because if a patient suffered from hypercortisolism – meaning that there was too much cortisol in their body, they could suffer from osteoporosis.

Secretion

Cortisol follows a diurnal pattern, a pattern which repeats daily. Throughout the day, cortisol’s levels differ: they increase the most just before waking up and they are at their lowest during the evening and after falling asleep.

Apart from this diurnal pattern, cortisol is secreted in response to stress and is nicknamed the “stress hormone”.

Regulation

Cortisol is regulated by the adrenocorticotropic hormone (ACTH), which is secreted by the anterior pituitary. However, in order for the adrenocorticotropic hormone to be synthesized, there's a few steps that have to be followed. First, the so-called corticotropin-releasing hormone (CRH) has to be secreted by the cells of the paraventricular nuclei in the hypothalamus, which gets a signal from the central nervous system that cortisol is needed. Corticotropin-releasing hormone then gets by the primary capillary plexus to the anterior pituitary and here it stimulates the secretion of adrenocorticotropic hormone, which in turn stimulates the secretion of cortisol. Of course, both ACTH and CRH follow cortisol’s diurnal pattern.

Negative feedback also plays a role in the regulation of cortisol because cortisol inhibits the secretion of the corticotropin-releasing hormone from the hypothalamus and it also decreases ACTH formation in the anterior pituitary. Remember, that the purpose of negative feedback is to ensure that we don’t have too much of the hormone. So, if there’s a lot of cortisol, cortisol itself is going to inhibit secretion of CRH and ACTH and that means that there’s not going to be too much of the hormone.

References:
Costanzo, L. S. (2018). Physiology. Elsevier.
Hall, J. E., Hall, M. E., & Guyton, A. C. (2021). Guyton and Hall Textbook of Medical Physiology. Elsevier.