Getting to know the HPA axis

In my last post, we discussed how a chemical and non-chemical stressor might interact to make a person more likely to experience an adverse health outcome. More specifically, we talked about how lead and psychosocial stress - particularly that related to socioeconomic status - could intersect via the hypothalamic-pituitary-adrenal (HPA) axis. Today, we will explore the HPA axis in more detail so that we can investigate other possible chemical/non-chemical interactions in future posts.

The HPA axis is an important part of the neuroendocrine system and is involved in our bodily response to stress. The HPA axis has three primary components - the hypothalamus, the anterior and posterior pituitary glands, and the adrenal cortex. The hypothalamus is a region of our brain that is involved in a variety of bodily functions, including the maintenance of temperature, sexual behavior, and autonomic functions like breathing. The pituitary gland is a component of the brain that is located proximal to the hypothalamus, and is often called the "master gland" because of its role in regulating many of the other endocrine glands. Finally, the adrenal cortex is located just above the kidneys on the periphery of the adrenal glands, and is involved in metabolic processes.


When a person faces a stressor, be it physical or emotional, the body reacts by stimulating the hypothalamus to release two neuropeptides - vasopressin (AVP) and corticotropin releasing hormone (CRH). Once released, AVP and CRH travel to the different parts of the pituitary gland, where they stimulate the creation and release of adrenocorticotopic hormone (ACTH). ACTH then enters the bloodstream, where it is carried to the adrenal glands, causing the adrenal cortex to produce glucocortiocids (GCs) from lipids such as cholesterol. In humans, the primary GC produced is cortisol, while in rats the primary GC is coricosterone. Glucocoritoids travel throughout the body (including the brain) and bind to two nuclear receptor hormones - glucocorticoid receptor (GR) and mineralocorticoid receptor (MR).

In the brain, GCs participate in a negative feedback loop (meaning that they control their own production) by binding to GR and MR in the hypothalamus. GCs also reduce the creation of ACTH in the pituitary glands by directly inhibiting the cleavage of proopiomelanocortin (POMC) into ß-endorphin and ACTH. The inhibition of ACTH formation in the pituitary glands and the binding of glucocorticoids to the GR and MR of the hypothalamus reduce the production of CRH, AVP, and ACTH, thereby reducing the amount of glucocorticoids that are produced.

The HPA axis is important for the regulation of immune, metabolic, and brain-related processes, and can be influenced by genetic/epigenetic background, rearing environment, and exposure to glucocorticoids in early life. Improper functioning and control of the HPA axis have been linked to immune-related diseases like rheumatoid arthritis and asthma exacerbation, decreased metabolic functioning associated with obesity and Cushing syndrome, and mood disorders such as major depression and anxiety disorders.


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