So DNA is basically just a cookbook of protein.RNA polymerase choose different selections of genes and transcribe them and they end up making proteins which make up dermal papilla cells.
RNA polymerase transcribes a section of DNA -- this section is a gene -- into RNA. And then sections of that RNA molecule is translated into a protein by ribosomes.
Here is a section from a textbook (Molecular Biology of the Gene) which you'll hopefully find helpful.
Using stem cells the dermal papilla cells construct the hair follicles. For some reason dermal papilla cells have lots of proteins which react to androgens, and since we have some type of correlation between hair loss and DHT we're pretty sure that for some reason the androgens destroy the dermal papilla cells and maybe like two other cell types that are also involved in the replication and maintenance of hair follicles.
Very few proteins react to androgens, but many proteins interact with the androgen receptor protein, which is activated when androgens bind to it. Activated AR can:
- bind DNA and change the rates of transcription of hundreds of genes (i.e. AR is a transcription factor)
- interact with other proteins and alter their function. So for example, AR is known to bind to the transcription factor beta-catenin and inhibit its activity or alter what genes it regulates. Since beta-catenin is essential for hair follicle regeneration, and AR has been shown to bind beta-catenin at a higher rate in dermal papilla cells from people with A.G.A. than in dermal papilla cells from fullheads, this interaction could be important.
Ultimately though, the mechanism of A.G.A. is unknown.
But it might not be the fault of the RNA polymerase for making too much AR protein, another gene that's some how specific to the hair on our scalps might be forcing it to.
Well, RNA polymerase is what actually transcribes the genes into RNA. A transcription factor can bind to DNA near a gene and sort of "open it up" to RNA polymerase. This will make RNA polymerase more likely to bind to the gene and transcribe it, therefore it will be more highly expressed. A transcription factor can also "close off" the sequence to RNA polymerase, and then the gene will be downregulated.
So then how did they measure the expression of AR in the GWAS?
If they took a bunch of people with hairloss, looked at the level of AR expression in their blood cells, saw that it was over expressed in comparison with full hair, but that there was no correlation with any other phenotype/illness, wouldn't that suggest that over expression of AR would only be associated with Androgenetic Alopecia and nothing else? Which doesn't make any sense since inhibiting the AR gene can cure forms of prostate cancer.
Surely you'd have to measure the expression of AR in the scalp, DPC's and so forth.
When you do a GWAS, this is what you do.
1) Take a bunch of people from a certain population, in this case British men.
2) Find what alleles (A, G, C, T) these people carry at a bunch of SNPs (single nucleotide polymorphisms) - let's say 1 million SNPs for example. These are single-letter parts of the genome for which there is variation in that population.
3) Split your population into two groups, one corresponding to one condition (in this case "bald") and one corresponding to the other (in this case "not-bald").
4) Find which SNPs are more commonly found in one group than the other. These are likely found near genes that contribute to the development of that condition.
So GWAS doesn't look at gene expression (mRNA/protein), it only looks at variation at the DNA level.
You said Lithium Chloride can turn the inhibtion of DHT??
Lithium chloride is a GSK3-beta inhibitor, which sort of mimics canonical Wnt signaling.
