Mr. Michael Barry,
Arguing with Mr. Foote is pointless. Current research clearly demonstrates what you believe to be true. Not only does current research demonstrate an increase in androgen receptor in balding scalp, but it also demonstrates differences at the receptor level and at the gene level when you compare balding scalp to non-balding scalp follicles and scalp follicles to beard follicles.
It is ridiculous to think that there isn't an intrinsic difference in follicles from different regions of the body. Especially, once a person reaches puberty. Scalp hair, body hair, and beard hair all obviously grow at different rates, so there is an obvious intrinsic difference at both the gene level and at the level of their response to androgens.
The following paper clearly demonstrates that androgens obviously have differing effects depending upon which follicle they influence.
J Invest Dermatol. 2006 Dec;126(12):2583-95. Epub 2006 Jun 29. Links
Differences in expression of specific biomarkers distinguish human beard from scalp dermal papilla cells.Rutberg SE, Kolpak ML, Gourley JA, Tan G, Henry JP, Shander D.
Gillette/P&G Technical Center, Needham, Massachusetts 02492, USA.
susan_rutberg@gillette.com
Androgen exposure stimulates the growth of beard hair follicles. The follicle dermal papilla appears to be the site of androgen action; however, the molecular mechanisms that regulate this process are not well understood. In an attempt to identify genes that contribute to the androgen-responsive phenotype, we compared gene expression patterns in unstimulated and androgen-treated cultured human dermal papilla cells isolated from beard (androgen-sensitive) and occipital scalp (androgen-insensitive) hair follicles. Through this analysis, we identified three genes that are expressed at significantly higher levels in beard dermal papilla cells. One of these genes, sfrp-2 has been identified as a dermal papilla signature gene in mouse pelage follicles. Two of these genes, mn1 and atp1beta1, have not been studied in the hair follicle. A fourth, fibulin-1d, was slightly upregulated in beard dermal papilla cells. The differences in the expression of these genes in cultured beard and scalp dermal papilla cells reflected similar differences in microdissected dermal papilla isolated from intact beard and scalp follicles. Our findings introduce potentially novel signaling pathways in dermal papilla cells. In addition, this study supports that cultured dermal papilla cells provide a cell-based model system that is reflective of the biology of in vivo hair follicle cells.
The next study clearly demonstrates a difference in androgen receptor co-activator activity in balding vs. normal scalp hair follicles.
J Invest Dermatol. 2007 May 17; [Epub ahead of print] Links
Androgen Receptor Co-Activator Hic-5/ARA55 as a Molecular Regulator of Androgen Sensitivity in Dermal Papilla Cells of Human Hair Follicles.
Inui S, Fukuzato Y, Nakajima T, Kurata S, Itami S.
1Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Androgen site-specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co-activators. To examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co-activator Hic-5/ARA55. Its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two-hybrid assays.
The semiquantitative reverse transcriptase-polymerase chain reaction showed that Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp. To determine whether Hic-5/ARA55 mRNA level correlates with its endogenous activity, we studied the effect of dominant negative Hic-5/ARA55 on transfected androgen receptor transactivation induced by R1881 using mouse mammary tumor virus-luciferase assays. We found that it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from the beard and bald frontal scalp, respectively, whereas it showed no significant effect in cells from the occipital scalp. Our findings suggest that Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles.Journal of Investigative Dermatology advance online publication, 17 May 2007; doi:10.1038/sj.jid.5700883
These studies don't even begin to describe the plethora of genes and proteins that are influenced by androgens.
This is a conversation that isn't even worth having right now. There is obviously a regulatory difference between scalp hair and hair from other regions of the body both before and after puberty and the regulation is directly influenced by androgen receptor mutation/concentration in normal/balding scalp.
By the way, Michael. The response to androgens is dose dependent and time dependent. I think that I've already posted this study before.
Skin Pharmacol Physiol. 2006;19(6):311-21. Epub 2006 Aug 23.Links
Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells.Winiarska A, Mandt N, Kamp H, Hossini A, Seltmann H, Zouboulis CC, Blume-Peytavi U.
Department of Dermatology and Allergy, Charité-Universitatsmedizin Berlin, Berlin, Germany.
Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5alpha-dihydrotestosterone (5alpha-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5alpha-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers.
T and 5alpha-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10(-5) M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5alpha-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5alpha-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10(-5) M. High concentrations of T and 5alpha-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.
Lastly, I think an important study to note is the following as it clearly demonstrates that there is a clear difference with regards to the external hormonal environment when it comes to particular regions of the scalp. There are only two ways that there can be such a clear difference. There is either more five alpha reductase in areas of the scalp that are more sensitive to balding or finasteride produces more SHBG in areas where it has its greatest effects. Personally, I believe both to be true.
Br J Dermatol. 2006 Apr;154(4):730-4. Links
Evaluation of androgens in the scalp hair and plasma of patients with male-pattern baldness before and after finasteride administration.Ryu HK, Kim KM, Yoo EA, Sim WY, Chung BC.
Bioanalysis and Biotransformation Research Centre, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-605, Korea.
BACKGROUND: Finasteride, a competitive inhibitor of the enzyme 5alpha-reductase II, is widely used as a medical treatment for patients with male-pattern baldness (male pattern baldness), which is affected by the distribution of androgenic steroids. It is also notable that the androgenic effect in male pattern baldness is different for each region of the head. OBJECTIVES: To study the effect of the drug finasteride, we quantified androgenic steroids in the vertex and occipital scalp hair and in the plasma of patients with male pattern baldness. METHODS: The patients with male pattern baldness, aged 23-52 years, were treated with finasteride 1 mg daily for 5 months. The hair and plasma samples were hydrolysed, extracted with n-pentane, and derivatized with MSTFA:NH4I
TE (1000:4:5, v/w/w). We analysed the concentrations of dihydrotestosterone (DHT) and testosterone (T) in the hair and plasma using gas chromatography-mass spectrometry (GC-MS). RESULTS:
In the hair, the ratio of DHT/T was decreased in the vertex scalp hair after the individual received finasteride (P < 0.005). However, we found no significant difference in the ratio of DHT/T in the occipital scalp hair before and after individuals received finasteride. Like the results in the vertex scalp hair, the ratio of DHT/T in the plasma was remarkably decreased after finasteride administration (P < 0.001).
CONCLUSIONS: This study supports the effect of finasteride in patients with male pattern baldness by examining the decreased level of DHT/T in scalp hair and in plasma. Thus, in view of the androgenic effect in the different hair regions, the vertex scalp hair plays a more important role for patients with male pattern baldness treated with finasteride than does the occipital hair.