The Cortisol Production Signaling Cascade

The signaling molecule ACTH is released by the pituitary gland in the brain and released into the bloodstream. When it reaches the adrenal cortex, it stimulates the production of cortisol. This particular signaling cascade is a great example of the complex ways that organelles do important jobs that are not often explored when generally defining their function. In the movie we see a simplified version of how it all works. Below is a description, including some of the details we left out of the movie.

ACTH Docks on an MC2-R Receptor* on a cell in the cortex of the adrenal gland.

*NOTE: The MC2-R receptor system looks and works similarly to the beta-2 adrenergic receptor system, which initiates relaxation of the bronchiole muscle cells (seen later in the movie) when epinephrine binds to it.


When it binds, ACTH stimulates the receptor to change shape. This conformational change causes the G protein complex to become activated and uncoupled.

G Protein

When the G protein stimulates it, Adenylate cyclase converts ATP (the cell's energy molecule) into cAMP (a signaling molecule).


cAMP activates Protein Kinase A. When cAMP binds to the regulatory subunits of Protein Kinase A (PKA), a conformational change occurs that releases its catalytic subunits (only one is shown here for simplicity).

PKA Active

The activated PKA subunit then travels to the mitochondrial membrane and switches on (phosphorylates) a protein called StAR (steroidogenic acute regulatory protein) There are actually several interacting proteins that work together to perform this specialized function in the adrenal cortex. Only one protein is shown here for simplicity. See for a diagram of the entire protein complex.

PKA to mitochondrian

StAR is responsible for mediating the complicated task of importing cholesterol into the mitochondrion.

cholesterol to mitochondrian

Once inside, enzymes perform two chemical conversions, turning the cholesterol into 17-OH-pregnenolone.

17-OH-pregnenolone is then sent to the endoplasmic reticulum, where it is converted into 11-deoxycortisol.


This compound is then sent back to the mitochondria where it is finally transformed into the final product, cortisol.


Cortisol freely crosses the membrane barrier and enters the bloodstream.


APA format:

Genetic Science Learning Center. (2020, July 31) The Cortisol Production Signaling Cascade. Retrieved April 15, 2024, from

CSE format:

The Cortisol Production Signaling Cascade [Internet]. Salt Lake City (UT): Genetic Science Learning Center; 2020 [cited 2024 Apr 15] Available from

Chicago format:

Genetic Science Learning Center. "The Cortisol Production Signaling Cascade." Learn.Genetics. July 31, 2020. Accessed April 15, 2024.