Glucocorticoids

The site of glucocorticoid production is primarily (but not limited to) the Zona Fasiculata. Some synthesis occurs in the Reticularis layer. They are involved in a number of physiological processes associated with metabolism including:

·         Gluconeogenesis

·         Fat and protein catabolism

·         The release of fatty acids and glucose into the blood

The actions of glucocorticoids, contary to what their name implies, are not limited to glucose mobilisation. In addition they can control aspects of the immune response for example:

·         Anti-inflammatory effects: protect against injury - They are used for Rheumatoid arthritis treatment and for the topical relief of swelling and inflammation associated with skin conditions e.g. eczema

·         They can suppress the immune system - Commonly used as immunosuppressants for post-transplant patients

The primary glucocorticoid produced by the adrenal cortex in humans is Cortisol. The primary substrate for the synthesis of cortisol (and for all other steroid hormones) is cholesterol.

Cortisol 

Structure

Very few structural differences exist between cortisol and aldosterone. Cortisol has an additional -OH group at position 17, and lacks the aldehyde group seen at positon 18 on aldosterone. It is these small differences that enable the glucocorticoid activity of cortisol that is not a property of aldosterone, certainly not at physiological concentrations

The structure of Cortisol. Image courtesy of https://upload.wikimedia.org/wikipedia/commons/5/5f/Cortisol.png under the terms of the GNU Free Documentation Liscense

Cortisol is often referred to as a “stress hormone”, due to its involvement in the stress response. In order to understand the role of Cortisol in stress, it is important to first consider the physiology of the stress response.

The Stress response

The response to stress is typically divided into three phases: 1. Alarm phase 2. Resistance phase 3. Exhaustion phase.

The alarm phase

The primary hormone involved in this phase is adrenalin. This mediates very rapid and short term responses to prepare the body for “fight or flight”.

The resistance phase

This is the phase we are concerned with when considering the hormones of the adrenal cortex in particular, cortisol. It is initiated in response to hypothalamic releasing hormones, which stimulate a biological cascade. For example:

The release of Cortisol from the adrenal cortex will mediate the body’s response to stress, and ultimately lead to the termination of the stress response through negative feedback. However if the stresses persist and worsen the exhaustion phase will set in.

Exhaustion phase

Eventually the adaptations to stress will break down. Prolonged exposure to the hormones involved in the resistance phase cause among other things, muscle wastage, and a failure to maintain electrolyte balance. If this persists, cumulative structural and functional damage to vital organs will occur.