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Different patterns of 5alpha-reductase expression


#1

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

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


#2

So fin is 5AR2 inhibitor, and they say that there mostly was 5AR1 not the 5AR2


#3

» So fin is 5AR2 inhibitor, and they say that there mostly was 5AR1 not the
» 5AR2

mk386 has been tested by merk for alopecia, but wasn’t really effective.


#4

Thats why it does not make sense. Or maybe the important cells are some other cells then the two types they mention


#5

» Thats why it does not make sense. Or maybe the important cells are some
» other cells then the two types they mention

alpha five type two is the important one to inhibit, whats not to understand. Even though there is more type one in the skin, its not the type that gets uptaken by the nucleus of the dermal papilla that starts the whole bad process.

about 77 percent of the androgen uptaken by the follicle is supposed to be dht, most of the rest is just testosterone—dht has a much slower dissassociation rate from the receptor than testosterone, so more androgen-inductible genes get expressed when dht binds. Dutasteride trials in Korea show that dutasteride pretty much stops further baldness…


#6

» alpha five type two is the important one to inhibit,
»

». Dutasteride trials
» in Korea show that dutasteride pretty much stops further baldness…

Isn’t this a contradiction Benji? Dut is type one not two.


#7

Is it possible that those who Finasteride dont help are simply “Type 1 5ar” ?

Also I wish they included eyebrows cells into their study.

They gave, in the end, a conclusion about beard cells , what about SDPCs (scalp hair : that what matters to us ) :

The 5alphaR1 inhibitor MK386 exhibited a more potent inhibitory effect on 5alphaR activity than finasteride (5alphaR2 inhibitor) in bDPCs


#8

» Is it possible that those who Finasteride dont help are simply “Type 1 5ar”
» ?
»
» Also I wish they included eyebrows cells into their study.
»
» They gave, in the end, a conclusion about beard cells , what about SDPCs
» (scalp hair : that what matters to us ) :
»
» The 5alphaR1 inhibitor MK386 exhibited a more potent inhibitory effect on
» 5alphaR activity than finasteride (5alphaR2 inhibitor) in bDPCs

saw palmetto has been shown to block both types 1 and type 2


#9

» » Thats why it does not make sense. Or maybe the important cells are some
» » other cells then the two types they mention
»
»
»
» alpha five type two is the important one to inhibit, whats not to
» understand. Even though there is more type one in the skin, its not the
» type that gets uptaken by the nucleus of the dermal papilla that starts the
» whole bad process.
»
» about 77 percent of the androgen uptaken by the follicle is supposed to be
» dht, most of the rest is just testosterone—dht has a much slower
» dissassociation rate from the receptor than testosterone, so more
» androgen-inductible genes get expressed when dht binds. Dutasteride trials
» in Korea show that dutasteride pretty much stops further baldness…

what is so different about DHT that is produced by 5ar1 and the DHT that comes from 5ar2 then? Or why would DP uptake just the type2 and ignore the type1 if both are present in there? are they somehow different really? or what the hell?

also somewhere I remember you mentioning that the balding scalp has less of receptors. Is that true? Or was it a mistake?


#10

I’ll try to help elucidate some of questions that seem to be arising due to this paper.

  1. 5-alpha reductase type 1 and 2 both convert testosterone into DHT. DHT then binds to the androgen receptor (AR) with high affinity, which allows it to go to the nucleus and bind to DNA turning on (or off) many other genes. Many of the genes that the AR activates can lead to the reduction of hair growth and is very likely the cause of hair loss. Dutasteride inhibits both type 1 and 2. Finasteride inhibits type 2 more specifically.

  2. Keratinocyte cells, which make up the majority of the hair follicle, as well as Sebocytes, which make the sebaceous gland also contain 5-alpha reductase. Unfortunately the article does not dive into these cell types but only covers the distribution of 5-alpha reductase in dermal fibroblasts. This is unfortunate because I believe the underlying problems in hair loss derives from follicle bulge region, which is composed of keratinocyte stem cells.

  3. 5-alph reductase was found in the cytoplasm and not in the nucleus. It is an enzyme that converts testosterone to DHT and does not initiate transcription (turns on genes) on its own, that I know of. As I mentioned, DHT can then bind to the AR which then goes to the nucleus and initiates transcription.

I hope that clears up a little of anyone’s confusion.

» 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
»
» 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


#11

» I’ll try to help elucidate some of questions that seem to be arising due to
» this paper.
»
» 1. 5-alpha reductase type 1 and 2 both convert testosterone into DHT. DHT
» then binds to the androgen receptor (AR) with high affinity, which allows
» it to go to the nucleus and bind to DNA turning on (or off) many other
» genes. Many of the genes that the AR activates can lead to the reduction of
» hair growth and is very likely the cause of hair loss. Dutasteride inhibits
» both type 1 and 2. Finasteride inhibits type 2 more specifically.
»
» 2. Keratinocyte cells, which make up the majority of the hair follicle, as
» well as Sebocytes, which make the sebaceous gland also contain 5-alpha
» reductase. Unfortunately the article does not dive into these cell types
» but only covers the distribution of 5-alpha reductase in dermal
» fibroblasts. This is unfortunate because I believe the underlying problems
» in hair loss derives from follicle bulge region, which is composed of
» keratinocyte stem cells.
»
» 3. 5-alph reductase was found in the cytoplasm and not in the nucleus. It
» is an enzyme that converts testosterone to DHT and does not initiate
» transcription (turns on genes) on its own, that I know of. As I mentioned,
» DHT can then bind to the AR which then goes to the nucleus and initiates
» transcription.
»
» I hope that clears up a little of anyone’s confusion.
»
»
» » 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
» »
» » 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

what is your comment on natural 5 ar inhibitors
i see comments on prop and dut, but none on natural dht blockers such as saw palmetto pygeum nettles pumpkin seed etc


#12

» what is your comment on natural 5 ar inhibitors
» i see comments on prop and dut, but none on natural dht blockers such as
» saw palmetto pygeum nettles pumpkin seed etc

I would say they can only help but they can also be a burden on your wallet too for not much effect. Dutasteride is by far the best thing out there right now for hair loss, in my opinion.


#13

» » what is your comment on natural 5 ar inhibitors
» » i see comments on prop and dut, but none on natural dht blockers such
» as
» » saw palmetto pygeum nettles pumpkin seed etc
»
» I would say they can only help but they can also be a burden on your
» wallet too for not much effect. Dutasteride is by far the best thing out
» there right now for hair loss, in my opinion.

they are not expensive at all the naturals, and a lot of guys are now combining them with prop

DUT while supposedly effective also has a lot of nasty side effects

if you have never tried naturals, I feel you are unqualified to comment on them


#14

How can you get Dutaseride (in America) if you need a prescription for it (I don’t have prostate problems).

This may be a silly question to some of you, but I don’t have any experience ordering pills (I usually just go to Walgreens).


#15

I have tried saw palmetto extract, grape seed extract, and nettle extract. I have also tried propecia, and minoxidil. I have formulated a lithium succinate with zinc sulfate lotion as well, and even tried zinc oxide for fun for a while too. All of those, except maybe the lithium that I didn’t try for long enough, showed little to no results (hence the comment on them being expensive for the results they deliver). Dutasteride has kept my hair line at the same place for 6 years now. All that said, I am definitely not qualified like a doctor is to make recommendations on anything, but this is simply a message board so I feel I am quite qualified to comment here especially on my own experiences.

» they are not expensive at all the naturals, and a lot of guys are now
» combining them with prop
»
» DUT while supposedly effective also has a lot of nasty side effects
»
» if you have never tried naturals, I feel you are unqualified to comment on
» them


#16

United Pharmacies www.unitedpharmacies.com

search around for Dutas or Duprost, those are the generic names for dutasteride.

» How can you get Dutaseride (in America) if you need a prescription for it
» (I don’t have prostate problems).
»
» This may be a silly question to some of you, but I don’t have any
» experience ordering pills (I usually just go to Walgreens).


#17

Dut demands a perscription. And it’s not officially approved for hair loss usage. It’s still on the market as a prostate drug.

I’ve surfed a lot of info and studies about all this stuff.

I don’t understand the cellular actions of most of it, but I kept reading long enough to get an idea about the bottom line.

When it comes to our skin and DHT: Hair loss is overwhelmingly a DHT#2 problem, and DHT#1 mainly causes the acne problems.


#18

Thanks.:slight_smile:


#19

» I have tried saw palmetto extract, grape seed extract, and nettle extract.
» I have also tried propecia, and minoxidil. I have formulated a lithium
» succinate with zinc sulfate lotion as well, and even tried zinc oxide for
» fun for a while too. All of those, except maybe the lithium that I didn’t
» try for long enough, showed little to no results (hence the comment on them
» being expensive for the results they deliver). Dutasteride has kept my hair
» line at the same place for 6 years now. All that said, I am definitely not
» qualified like a doctor is to make recommendations on anything, but this is
» simply a message board so I feel I am quite qualified to comment here
» especially on my own experiences.
»
» » they are not expensive at all the naturals, and a lot of guys are now
» » combining them with prop
» »
» » DUT while supposedly effective also has a lot of nasty side effects
» »
» » if you have never tried naturals, I feel you are unqualified to comment
» on
» » them

a lot of guys have had results with DUT, a lot have not, a lot have also had nasty side effects. This doesnt mean DUT is good or bad…or better or worse than naturals
however just because you had good results with DUT doesnt make it good. or just because you did not respond to naturals, does not make them bad

we all react to different regimens

I do see you though, acting like your experience with DUT, by itself , makes DUT out to be some sort of savior, and it is far from that

I never claim naturals work on everyone, but they do work well on a lot of guys, and cannot be brushed to the side

if you were using saw palmetto that was not standardized, you might well have been seeing poor results because of that…non standardized saw palmetto you have no way of knowing what dose you are getting


#20

Well good luck with your regimen, and I’m glad everyone that it is working for is getting good results. I’m just presenting my own views here not trying to get into a trolling fight–take them as you wish.

» a lot of guys have had results with DUT, a lot have not, a lot have also
» had nasty side effects. This doesnt mean DUT is good or bad…or
» better or worse than naturals
» however just because you had good results with DUT doesnt make it good. or
» just because you did not respond to naturals, does not make them bad
»
» we all react to different regimens
»
» I do see you though, acting like your experience with DUT, by itself ,
» makes DUT out to be some sort of savior, and it is far from that
»
» I never claim naturals work on everyone, but they do work well on a lot of
» guys, and cannot be brushed to the side
»
» if you were using saw palmetto that was not standardized, you might well
» have been seeing poor results because of that…non standardized saw
» palmetto you have no way of knowing what dose you are getting