5alphareductase (5ARase) inhibitors such as Finasteride and Dutasteride block the intracellular conversion of testosterone to dihydrotestosterone (DHT), and they have both been shown to reduce male pattern hair loss
When taken orally the reduced circulating blood levels of DHT, are associated with a reduced libido in many people, so this opens the possibility of using Finasteride and possibly Dutasteride topically so that there is little or no drop in circulating DHT levels.
However the question I would like help with is - is the effect of DHT on hair follicles primarily due to the intracellular conversion of Testosterone or is circulating DHT more important?
This is important because if circulating levels are important then it suggests that topical applications of finasteride/dutasteride will not work effectively and that testosterone receptor blockers applied topically would work better
For Reference - Normal testosterone levels in male adults are approx 10-30nmol/L, most of which is bound to circulating proteins, with only a small proportion present in free state. By comparison DHT range is in the region of 0.4 to 2nmol/L though there is no standard reference range and it is unclear how much of this is unbound
I think that both circulating testosterone and intracellular conversion of testosterone are important for hair loss due to:
1. In the blood vessels more than 97 % of the testosterone is bound to plasma protein and cannot cross the blood vessels walls due to its size. 3% of the male hormone circulates in the blood as free male hormone, due to its small size it can cross the blood vessels walls in to the tissues including scalp tissues. In the scalp tissues male hormone testosterone enter into hair follicle cells mainly the papilla cells, outer root sheath cells and sebaceous gland and get converted into DHT (Di-hydro-testosterone) by an enzyme 5 alpha reductase. The DHT in the outer root sheath cells, papilla cells and pilosebaceous cells of hair bind to Androgen Receptors in the cytosol. This DHT Androgen receptor complex is able to enter into the cell nucleus and bind to DNA , it leads to production of cell specific messenger RNA ,which help in the synthesis of specific follicle damaging proteins, leading to the progressive miniaturization of hair with each successive hair cycle, and eventually hair loss.
2. Testosterone can get converted into DHT in the blood circulation. The circulating DHT in the blood enter in the tissues including scalp tissue. In the scalp tissue DHT enter into hair follicle cells, mainly the papilla cells, outer root sheath cells and sebaceous gland cells. DHT might bind to different receptors rather binding to Androgen Receptors in the cytosol of papilla cells , outer root sheath cell and sebaceous gland cells and enter into the nucleus and bind to the DNA leads to production of cell specific mRNA and synthesis of specific proteins that lead to progressive miniaturization of hair and hair loss. As these alternate pathways does not involve 5 alpha reductase, finesteride is not effective.
As you know, finasteride is an oral drug that effectively inhibits 5alphareductase. In fact, oral administration of finasteride is more effective than topical application. Because topical application of finasteride depends on its penetrability into skin.
I really want to discuss with you about this field.
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