A New Method of Drug Synthesis: Yeast as Steroid Factories
Glucocorticoids

 

         Synthesis of glucocorticoids in yeast is a worthwhile endeavor because these compounds are used for a wide range of theraputic purposes. Below is a description of how glucocorticoids work in humans and how they are used to treat disease.  

Glucocorticoid Physiology

  • Glucocorticoids are a class of steroid hormones produced in the adrenal cortex.
  • Glucocorticoid production in the adrenals is stimulated by adrenocorticotropic hormone (ACTH), which is made by the pituitary gland.

Figure 2A: ACTH secreted by the pituitary gland travels to the adrenal cortex and stimulates hydrocortisone synthesis.

Glucocorticoids Regulate Metabolism

Glucocorticoids get their name from their effect of raising blood sugar (glucose). This is done by stimulating gluconeogesis (glucose synthesis) in the liver. Hydrocortisone is the most abundant glucocorticoid in the body.

 

Glucocorticoids Supress Inflammation

Hydrocortisone and other glucocorticoids have strong anti-inflammatory and immunosuppressant effects on the body. For this reason, they are used to treat the following conditions:

  • Reduction of inflammation in rheumatoid arthritis, lupus, and other autoimmune diseases
  • Relief of asthma symptoms
  • Prevent rejection of transplanted organs

Figure 2B: Inhaled glucocorticoids are an effective treatment for reliving symptoms of asthma.

 

Glucocorticoids Induce Gene Expression

The mechanism of glucocorticoid action is as follows:

  1. Glucocorticoids pass through the plasma membrane (they are hydrophobic) and get inside the cell.
  2. Glucocorticoid binds glucocorticoid receptor in the cytosol.
  3. Glucocorticoid-GC Receptor complex enters the nucleus and induces transcription of specific genes.
  4. Gene products regulate inflammation.

Figure 2C: Glucocorticoids regulate inflammation by activating transcription in the nucleus.

 


Steve Tilley  steve_tilley@yahoo.com 
Biochemistry 462b Honors Project, 2003  The University of Arizona 
Last Revised: May 07, 2003