Hair growth and epidermal growth factor receptor (EGFR)

Dermatol Online J. 2009 Mar 15;15(3):1.
The cutaneous epidermal growth factor network: Can it be translated clinically to stimulate hair growth?
Alexandrescu DT, Kauffman CL, Dasanu CA.

Georgetown Dermatology, Washington, DC, USA. mddoru@hotmail.com

The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss.

Dermatol Online J. 2009 Mar 15;15(3):4.
Persistent hair growth during treatment with the EGFR inhibitor erlotinib.
Alexandrescu DT, Kauffman CL, Dasanu CA.

Georgetown Dermatology, Washington, DC, USA. mddoru@hotmail.com

Medications belonging to the group of epidermal growth factor (EGFR) inhibitors are currently in widespread use for the treatment of epithelial malignancies. Many cutaneous side effects are known to develop as a result of the use of these agents. Trichomegaly is a newly described side effect, consisting of premature maturation (terminal differentiation) of the hair of the eyelashes and the scalp, which is characterized by a hairy phenotype. Although occurrence of the acneiform skin rash is clearly associated with favorable tumor responses and improvement in patient survival during the use of EGFR inhibitors for the treatment of cancer, the significance of trichomegaly is less clear. A review of all published cases is provided, leading to the observation that trichomegaly also developed in patients whose tumors had a positive response to anti-EGFR therapy. The apparent lack of the development of tolerance to this medication effect and, therefore, the continued clinical sign of trichomegaly is in contrast to the time-limited nature of other cutaneous side effects of EGFR inhibitors, such as the classical papulo-pustular rash. The persistence of trichomegaly in some patients brings into question the precise mechanism of this phenomenon and suggests the possibility of using EGFR inhibition therapeutically to stimulate hair growth.

What is a natural epidermal growth factor (EGFR) inhibitor?

Genistein, a soy isoflavone, Curcumin, Resveratrol and Quercetin.

CS, I see that Curcurmin has a mulitude of positive effects, regarding inflammation,
and in this case, hair growth. Curcumin as we all know has been consumed for
probably centuries. Why is it only now coming into the hair loss arena? Is it because
of absorbtion factor in the gut or the dose size consumed was previously too small to be effective ?
Its effectiveness seems to be dose dependent. Is there such a thing as too much ? LEF
and others continue to improve absorption where 1 pill is now the equivelent of previously
many. I take BCM-95 2 p/d and I think it seems to reduce inflammation somewhat further
then without it, but it would be a nice extra if it encourages growth of terminal type hairs
given that regrowth for many is confined to mostly vellous type hairs.....

2560 - Curcumin was first known in 2001 to be an inhibitor of DHT.

http://www.ncbi.nlm.nih.gov/pubmed/11380153

The focus back then was almost entirely on DHT, and the myriad of other mechanisms were not entirely understood, either with respect to hair growth or to the actions of curcumin.

Several years ago I was first intrigued to learn that only 2% of India's 60 + age-group ever contracted Alzheimer's disease. But only recently Alzheimer's has been connected with a description of "Diabetes type 3." Also researchers now understand that Alzheimer's is simply inflammation of the brain. Naturally the curry spice (Turmeric/Curcumin) comes to mind as the reason.

There's been an explosion of research on curcumin recently. Just a few short years ago, everything in the medical literature on Curcumin was primarily focused on its effects on various cancers, arthritis, etc.

The patent on Curcumin & Resveratrol drew more attention. But now a very recent study (April 2009) posted on this forum revealed that Curcumin & Resveratrol polyphenols "act as neutral antagonists, producing no effect when tested alone while competitively antagonizing CB1 agonist..." To put this in the proper context, I'm quoting from the study below and it is referring to Cannabinoid receptors.

http://jpet.aspetjournals.org/cgi/reprint/jpet.109.151654v1

Cannabinoid receptors refer to receptors for endocannabinoids, and these were first indentified from Weed (C. Sativa), although technically doing weed would be considered exocannaibinoids. When we are under stress the temperature changes you feel on your scalp (heat or cold-clammy effect) are a result of stress reactions which are producing endocannabinoids (think of neuropeptides). Recently, endo & exocannabinoids have been identified as negative regulators of hair growth.

That said, blocking the CB1 receptor during these moments can spare your hair. Curcumin & Resveratrol when used together can accomplish this. I posted earlier that Cayenne can also block the CB1 receptor, but I think the collective "jury" (us) still needs time to evaluate its effects. To make matters a little more complicated, using both Curcumin & Cayenne together may compromise glucorinidation, so I'm personally a little hesitant to use both.

Over the last year and this year, the studies on Curcumin are covering a whole new area previously unexplored which happen to help with some of the later concepts of hair growth regulation. This includes transient receptor potential vanilloid type-1, balances to stress/adrenal system, GSK-3beta inhibition and more.

I have one theory on a question I get a lot - "Why does one temple thin out worse than the other?"

My theory: Whatever side of the brain is dominant with respect to emotions relating to neuropeptides (cannabinoid release) could be the reason.

CS, excellent informative post. Its appreciated by all!

Thanks you.