Astressin B: The Accidentally Discovered Cure for Stress-Induced Baldness in Mice

In researching compounds that may alleviate the effects of Cushing's Syndrome (symptoms from prolonged exposure to the stress hormone cortisol), the team of L. Wang, M. Million et al. made a significant discovery in using synthesized astressin-B on balding young mice that were genetically engineered to produce more cortisol. Baldness or alopecia has been linked to extreme stress, and the biochemical pathway involves several compounds.

(image from http://journal.frontiersin.org/article/10.3389/fneur.2013.00021/full)

When we perceive stress, the hypothalamus in our brain produces corticotropin-releasing hormone (CRH) which signals the nearby anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). This travels through the bloodstream to the adrenal cortex (the outside part of the adrenal gland that sits above the kidneys) and stimulates it to produce cortisol, a steroid molecule:

  Cortisol (By Calvero. [Public domain], via Wikimedia Commons

Steroids are easily identified by this 4-ring system - three of them have 6 carbons, and one has 5 carbons.

 Since CRH is the chemical key that starts this process, we should take a look at the complexity of its structure which has been designed by evolution:

 (image from chemBlink, http://www.chemblink.com/products/86784-80-7.htm)

A rather long strand of 41 peptides

So how does astressin B work in all of this and help prevent baldness in mice? The above mentioned authors (from the David Geffen School of Medicine and the Salk Institute for Biological Studies, respectively) collaborated with their team to see how this molecule can act as an agonist to CRH and thereby alleviate the symptoms of elevated stress in mice genetically engineered to overexpress CRH. What they discovered was a noticeable increase in hair growth after only 5 days of treatment with astressin B (5 micrograms intraperitoneal injection/day/mouse).

 

(image from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0016377)

Row A mice were injected with a saline solution; row B mice were injected with astressin B and are shown 3 days later; row C mice are the same mice from row B, 4 weeks later)

So what does astressin look like? As you can imagine, it is similar to CRH in that it is also a rather long polypeptide:

Resources:

*Wang L, Million M, Rivier J, Rivier C, Craft N, et al. (2011) CRF Receptor Antagonist Astressin-B Reverses and Prevents Alopecia in CRF Over-ExpressingMice. PLoS ONE 6(2): e16377. doi:10.1371/journal.pone.0016377