ACTH and Cortisol: The Hypothalamic-Pituitary-Adrenal Axis Explained

Quick take

The video explains how hypothalamic CRH stimulates the pituitary to release ACTH, which then prompts the adrenal cortex to produce glucocorticoids like cortisol. It also covers feedback loops and the broad metabolic and immune effects of cortisol.

• CRH from the hypothalamus triggers ACTH release from anterior pituitary
• ACTH binds MC2R on adrenocortical cells and stimulates cortisol synthesis
• Cortisol orchestrates glucose metabolism and dampens inflammation
• Glucocorticoids provide negative feedback to limit ACTH secretion

Overview of the hypothalamic-pituitary-adrenal axis

The Osmosis video provides a step by step view of how the hypothalamus controls the pituitary, which in turn regulates the adrenal glands. It emphasizes the central role of the hypothalamic pituitary axis in coordinating the body’s response to stress and maintaining metabolic balance. The discussion begins with corticotropin releasing hormone (CRH) from the hypothalamus and continues through adrenocorticotropic hormone (ACTH) release, adrenal stimulation, and the downstream production of corticosteroids, primarily cortisol, by the adrenal cortex.

In this hormonal cascade, CRH is released into the hypophyseal portal system connecting the hypothalamus to the anterior pituitary. The ACTH producing corticotroph cells respond to CRH by secreting ACTH inside granules, where it is stored until release into the bloodstream. A key biochemical detail is that ACTH is derived from a large precursor called Preproopiomelanocortin or PRE POMC, which includes a signal peptide that is cleaved to form propiomelanocortin or POMC, from which ACTH is ultimately generated.

"ACTH is synthesized from a large precursor molecule called Preproopiomelanocortin or PRE POMC" - Osmosis