Cell Receptors are the Key To Understanding Retinoids

At the American Academy of Dermatology Annual Meeting in San Francisco, Dr. Sewon Kang presented some of his prolific research on retinoids. The thing that I liked the most about his speech was his definition of a topical retinoid:

"any molecule that, by itself or through metabolic conversion, binds to and activates the retinoic acid receptors, thereby eliciting transcriptional activation of retinoic acid-responsive genes that results in specific biologic responses (Kang & Voorhees. Fitzpatrick's Dermatology in General Medicine [7th Ed.]. 2008)."

He went on to further explain that Vitamin A enters the skin where it is stored and esterfied. It is then oxidized into retinoic acid where it is received in the nucleas of the cell. (For a visual representation of this event click here).

He went on to point out that keratinocytes are divided faster in retinoid treated skin which is the main reason to use a retinoid.

There is also a general misconception that retinoids thin the skin. In a study that was conducted by Dr. Kang, skin biopsies show that the skin doubled in thickness.

The last thing he pointed out was, "Topical retinol elicits a retinoic acid-like epidermal histology (hyperplasia and spongiosis), but, unlike retinoic acid, it doesn’t cause significant erythema."

Therefore, it is my hope that we can get doctors to think about carrying an over the counter retinol as a great alternative to prescription strength retinoids.

You can read the full Dermatology Times article here.

Comments

[Bill]

A few things:

"He went on to point out that keratinocytes are divided faster in retinoid treated skin which is the main reason to use a retinoid."

Faster dividing keratinocytes are only of use to the extent that they cause transient smoothing and reduce cellular atypia. Partially because of the next point ...

"There is also a general misconception that retinoids thin the skin. In a study that was conducted by Dr. Kang, skin biopsies show that the skin doubled in thickness.""

Of course it "doubled in thickness" over the course of the 6 month study Kang did. Longer term studies reinforce again and again that epidermal hyperplasia takes place in the first 6-12 months. After that initial period, the epidermis retreats to baseline, actually a little thinner, around the same time the stratum corneum becomes looser again.

In contrast, the dermal repair zone of collagen seems to thicken around month 10-12, gradually increasing thereafer to about double tickness around month 24. Whether this thicekning of the DRZ offsets the eventual thinning of the epidermis for a net thickening is an open question.

In addition, retinoids inhibit/destroy certain structural components of the epidermis, desmosomes. Studies on this have been short term, and thus I don't know how this plays out long term.

In short, every treatment on retioids, even/especially from the Michigan docs, who have done some really interesting research, seems to indicate that the treatment is a universal good. In biology there are seldom free rides. If someone wants to prove retinoids as an anti-aging panacea, one would need to gauge net skin thickness past 12 months of treatment, as well as determine what structural components of the skin are down-regulated as collagen I and III are up-regulated again past 12 months).

[Kevin Katechis]

Wow, don't know how I missed this post, but would certainly like to address some of the questions you raised (sorry its late).

I need some help though to address your assertions to better to comment "the epidermis retreats to baseline, actually a little thinner" I have not seen this statement made in any of the studies I have read. Though I would agree studies over 12 months would be very beneficial. Therefore, I can only submit to you 20+ of observational data would contradict that statement.

I think your statement of destroy desmosomes is a bit overboard...inhibit is open for debate. Again, if you can supply the citation, I would be happy to review it.

I agree there are no free rides in biology, but I must also point out that there are alot of things we don't fully understand about how retinoids work from a scientific standpoint...all we have to go on is what is known (from a clinical standpoint) and what is observed over a twenty year time frame. My goal is to one day supply the data we need to help answer these questions.

Thank you for your observations and input.