Different patterns of 5alphaR expression in DP cells

[bornthisway]

Different patterns of 5alpha-reductase expression, cellular distribution, and testosterone metabolism in human follicular dermal papilla cells

Biochem Biophys Res Commun. 2008 Apr 18;368(4):858-64.
Liu S, Yamauchi H.
Research Department, Saitama Daiichi Pharmaceutical Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057, Japan.

Androgens regulate hair growth, and 5alpha-reductase (5alphaR) plays a pivotal role in the action of androgens on target organs. To clarify the molecular mechanisms responsible for controlling hair growth, the present study presents evidence that the human follicular dermal papilla cells (DPCs) from either beard (bDPCs) or scalp hair (sDPCs) possess endogenous 5alphaR activity. Real-time RT-PCR revealed that the highest level of 5alphaR1 mRNA was found in bDPCs, followed by sDPCs, and a low but detectable level of 5alphaR1 mRNA was observed in fibroblasts. Minimally detectable levels of 5alphaR2 mRNA were found in all three cell types. A weak band at 26kDa corresponding to the human 5alphaR1 protein was detected by Western blot in both DPCs, but not in fibroblasts. Immuonofluorescence analysis confirmed that 5alphaR1 was localized to the cytoplasm rather than in the nuclei in both DPCs Furthermore, a 5alphaR assay using [(14)C]testosterone labeling in intact cells revealed that testosterone was transformed primarily into androstenedione, and in small amounts, into DHT. Our results demonstrate that the 5alphaR activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17beta-HSD rather than 5alphaR among the three cell types. The 5alphaR1 inhibitor MK386 exhibited a more potent inhibitory effect on 5alphaR activity than finasteride (5alphaR2 inhibitor) in bDPCs.

PMID: 18258185

 

[harold]

This was an interesting study because the expression of 5ar-2 was very low in all the hair types looked at. Not quite sure what to make of it...
hh

 

[michael barry]

most of the DHT that gets uptaken by the DPC's is converted by the alpha five reductase type two enzyme located in the innermost portion of the outer root sheath according to Dr. David Whiting. His paper is in the hairlosstalk library.

 

[Bryan]

This was an interesting study because the expression of 5ar-2 was very low in all the hair types looked at. Not quite sure what to make of it...

You shouldn't be surprised at those results, because this is by no means the first time I've addressed the issue of these conflicting studies. Several times in the past I've mentioned an important study done by my favorite hairloss researchers. Here's a brief excerpt:

"Finasteride is the main inhibitor of 5alpha-reductase activity in microdissected dermal papillae of human hair follicles", Rolf Hoffmann and Rudolf Happle, Archives of Dermatological Research (1999) 291:100-103.

"...Our results showed that even 10 nM of finasteride completely inhibited 5alpha-reductase activity in all dermal papillae investigated. These results were reproducible in all experiments. MK-386 (maximum concentration 1 micro-mole/l), however, did not consistently inhibit or increase 5alpha-reductase in dermal papillae. In fact, for MK-386 no clear dose-relationship was apparent."

As you can see, Happle & Hoffmann's earlier results strongly contradict what was found in this new study. Furthermore, they were smart enough and honest enough to admit that their results even contradicted older studies that had already been done prior to their 1999 trial. They suggested that what _may_ possibly account for the discrepancy is that they (Happle & Hoffmann) had used FRESHLY DISSECTED hair follicles, as opposed to hair follicles that had been in storage for a while. They seemed to think that the expression of certain important genetic factors can change over time in storage, which is why they wanted to use hair follicles that were as FRESH as possible, to get the most accurate results.

Indeed, there's another fairly recent Japanese study which found that human hair follicle dermal papillae start to lose their ability to express the 5a-reductase type 2 enzyme in culture, but they express it just fine in situ. That suggests that Happle & Hoffman were right to use freshly-dissected hair follicles, and their results are more accurate than the other researchers who weren't so careful with their experimental procedures.