Cortisol Modulation

Cortisol

Cortisol is a hormone that modulates many physiological and psychological processes. Because of its central role in the body’s response to stress, cortisol is most commonly known as the stress hormone.  It plays a key role in regulating metabolism and maintaining normal blood pressure. It affects both cognition and emotional state. Cortisol also influences bone formation and density and suppresses the body’s immune response.

Hypercortisolism

Hypercortisolism is a disorder caused by excess cortisol activity. The use of steroid medications can cause hypercortisolism, as can the body’s overproduction of cortisol, usually caused by a noncancerous tumor. Chronic hypercortisolism can be harmful in many ways (see figure below). Psychiatric manifestations can include anxiety, depression, psychosis, disturbed sleep, and impaired memory. Physical manifestations can include impaired glucose tolerance, obesity, hypertension, and osteoporosis. Hypercortisolism can also impair the immune system and cause gonadal dysfunction.

Because cortisol is an important regulator of so many bodily functions, persistently elevated cortisol levels or dysregulation of its normal release patterns can cause serious illness.

Cortisol Modulation

Extensive research indicates that modulating cortisol’s activity at the glucocorticoid receptor (GR) may provide treatments for many serious disorders.  Binding of cortisol to the GR increases the expression of some genes, and decreases the expression of others. For example, the metabolic effects of cortisol, such as the stimulation of gluconeogenesis (creation of sugars in the blood), are caused by cortisol’s activation of gene transcription mediated through GR.

Corcept and its collaborators are studying the role of cortisol and cortisol modulation in patients with Cushing syndrome; pancreatic, prostate, ovarian, triple-negative breast, and lung cancer; NASH; and weight gain induced by antipsychotic medications.  Additional areas in which research has been conducted include diabetes; hypertension; osteoporosis; obesity; addictive disorders; central serous chorioretinopathy; Alzheimer’s disease; anxiety; neurodegenerative diseases; and posttraumatic stress disorder.