HPA-axis

not done nuclear adrenal steroid receptors

What is the primary role of the HPA axis in the body?

The HPA axis regulates stress response, circadian rhythms, and is involved in neurodegenerative diseases.

What three components make up the neuro-endocrine system related to the HPA axis?

• Hypothalamus

• Pituitary gland

• Adrenal glands.

What is the response to stress in the HPA-axis?

• Increased release of CRF from the hypothalamus

• Stimulates the pituitary glands to increase ACTH secretion

• Leads to increased cortisol and adrenaline release from the adrenal glands

Contributes to the Fear-Flight-Fight response by increasing heart rate/blood pressure etc

What is CRH and what role does it play in the HPA axis?

Corticotrophin-releasing hormone (CRH) stimulates the release of ACTH from the anterior pituitary. This then stimulates the adrenal glands to secrete hormones.

What does HPA hyperactivation in depressed patients indicate?

It indicates elevated levels of cortisol and CRH, and an increase in size and activity of the pituitary and adrenal glands.

The HPA is hyperactivated due to reduced negative feedback → more cortisol.

What are the effects of chronic stress on cognitive function?

Chronic stress may impair memory, increase anxiety and lead to neurodegeneration (stress increases receptor activation in the locus coeruleus leading to overactivation of neurones) or cardiovascular disease.

How does the circadian rhythm influence the function of the HPA axis?

In the adrenal cortex, CLOCK genes increase sensitivity of adrenal cells to ACTH typically in the morning. Leads to increase in cortisol.

What is the significance of the Locus Coeruleus in Alzheimer's disease?

The Locus Coeruleus is degenerated in Alzheimer’s disease.

It is the major source of noradrenaline in the brain, so degeneration leads to reduced ability to control brain inflammation, increased amyloid plaques and eventually the Alzheimer’s phenotype.

What is the location and function of the adrenal glands

Located above the kidneys

Small endocrine glands with two functionally different components

• Medulla (inner): produces catecholamines for release into the blood

• Adrenal Cortex (outer): produces glucocorticoids (cortisol) and steroid hormones (made from cholesterol)

Where is the Locus Coeruleus

The brain stem