Okey dokey, good point raised by almcg2:
5-alpha-reductase P450 is present in two flavors in humans: isozyme types I and II.
Characterization, expression, and immunohistochemical localization of 5 alpha-reductase in human skin. Luu-The V, Sugimoto Y, Puy L, Labrie Y, Lopez Solache I, Singh M, Labrie F. J Invest Dermatol.(1994) 102(2):221-6.
Human skin has been shown to contain a high level of 5 alpha-reductase activity, the enzyme that catalyses the conversion of the weak androgen testosterone into dihydrotestosterone, the most potent androgen. Because two types of 5 alpha-reductase genes have been characterized in humans, we have cloned 5 alpha-reductase cDNAs from adult human keratinocyte and skin fibroblast cDNA libraries to identify and gain better knowledge of the 5 alpha-reductase expressed in normal human skin. Nucleotide sequence analysis shows that the clones obtained correspond to the type I 5 alpha-reductase.
RNase protection analysis using (poly A)+ RNA obtained from human skin and prostate also confirms that type I 5 alpha-reductase is the predominant type expressed in normal skin, whereas type II 5 alpha-reductase is the major form found in the prostate. Following polymerase chain reaction amplification of human keratinocyte and skin fibroblast cDNA, a low level of type II 5 alpha-reductase cDNA has been detected. Using antipeptide antibodies raised in rabbits against the peptide sequence covering amino acids 227 -240 to perform immunohistochemical localization of 5 alpha-reductase, we have found that 5 alpha-reductase is distributed in
sweat and sebaceous glands, as well as in the epidermal cell layers, thus providing the basis for the important role of androgens in human skin and its appendages.
Pilosebacous glands are colocated in the same pores as hair follicles. This
article
yaks in technical jargon about the androgen binding site differences between the two types of isozymes present in a prostate hyperplasia cell line used for research on prostate disease.
What it shows is that both forms of isozyme are expressed in abnormally dividing prostate cells, and we know from our molecular biology primers, that this also means that there is unusual 5-alpha-reductase activity present, and that means tissue specific variable expression of the enzyme, and therefore, the localized tissue concentration of DHT.
Note that the type II isozyme is expressed at very low rates in skin, and high rates in prostate.
This fact, correlated with the differences in binding stength, and therefore, enzyme sensitivity to androgen type, answers your question.
Yes, if you have high circulating levels of DHT, you may exhibit MPB. But, if you have a tumor type that has the opposite isoform as the predominant type of alpha reductase enzyme present, it, and the androgen receptor cell surface concentration (and abberations of AR are possible as well) will determine if you have both MPB and prostate hyperplasia co-symptoms.
So, MPB is a general indicator, not a specific one, for potential response to androgen receptor upregulation. Furthermore, there is
no direct genetic evidence for MPB as a directly inherited trait within families.
Later reports link MPB to androgen receptor polymorphism (expression variation for the androgen receptor protein).
Polymorphism of the androgen receptor gene is associated with male pattern baldness. Ellis JA, Stebbing M, and Harrap SB. J Invest Dermatol. 2001 116(3):452-5.
Certain androgen receptor polymorphisms are apparently related to prostate disease susceptibility, when coupled to
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10334972insulin insensitivity - a known regulator of lipids in humans. And it has been linked to faulty nuclear receptor control of
vitamin D biosynthesis in the liver.
These are all cytochrome P450 catalyzed reactions.
To bring us our eye glazing discussion full circle, when you use anabolic steroids in supraphysiological concentrations, you saturate many nuclear receptors in liver, skin, prostate and breast tissue, plus brain. These nonspecific targets are then changed from natural regulatory contols...
and molecular mayhem results. Liver lipid and immune system dysregulation, upregulation and enhanced sensitivity to xenobiotic contaminants, etc.
Do you understand my arguments and explanations?
You are now at the cutting edge of knowledge on prostate hyperplasia, the precursor condition to tumor formation. Plus, you have an inkling of the connection between LXR and RXR, as well as PXR and SXR nuclear receptor swamping by anabolic steroids and their linkage to alterations in lipids (including those that affect oil production and skin cell inflammation and overgrowth) in both hair and skin negative sides associated with AAS use.
Now that wasn't so painful...was it? *laughing*