Cushing's syndrome and the hypothalamic-pituitary axis

Glucocorticoids (GCs) refer to receptor-specific steroid hormones acting on glucose metabolism, binding to the GR (glucocorticoid receptor). The process of GC signaling involves a molecule composed of glucose, a cortex, and a steroid. GCs are produced in various responses mediated by neuroendocrine and endocrine signals along the HPA (hypothalamic-pituitary-adrenal axis).

Figure 1. The HPA (hypothalamic-pituitary-adrenal axis)

Under normal conditions, the hypothalamus sends corticotropin releasing hormone (CRH) to the anterior pituitary gland. The CRH then stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). The ACTH then stimulates the adrenal cortex, located above the kidneys, to secrete cortisol. Cortisol in the blood will normally regulate the hypothalamus and anterior pituitary production of CRH and ACTH respectively through negative feedback inhibition.

Cushing’s syndrome results from excessive levels of cortisol circulating in the body for extended periods of time. This can be caused by taking medicinal glucocorticoids, such as prednisone, for the treatment of asthma, lupus and other autoimmune diseases. Cushing’s syndrome is similar to Cushing’s disease, however, in Cushing’s Disease, hypercortisolism is resulting from the overproduction of ACTH from the pituitary. This could be caused by either a pituitary adenoma or a non-pituitary tumor.

In humans, the symptoms of Cushing’s syndrome can vary between individuals. The classic signs of Cushing’s syndrome in humans include: rounded face, upper body obesity, fat deposits on neck, and thin arms and legs.

To study the effects of the hypothalamo-pituitary-adrenal axis, groups of mice were injected with different hormones. Group A mice were injected with cortisol to mimic effects of Cushing’s syndrome. Group B mice were injected with hormone X. Group C mice were injected with a saline solution. Blood samples were later taken from the various groups and average hormone levels were measured and recorded in Table 1.

Table 1. Levels of hormones (in nmol/L) found in blood sample taken from experimental mice groups.

Data adapted from: Cushing's Disease. UCLA Pituitary Tumor Program, Pituitary Tumor Surgery