5 month results w/Miconazole Nitrate + Minoxidil - photos

[rwhairlosstalk]

I see they don't check date of births on here. There are immature adults born every minute.

This thread was a good confirmation of MN.

 

[Rogazzle]

Here we are 7 weeks in after starting finasteride .5mg/day.

Pics and labels speak for themselves.

Click to expand images.

Before

After

 

[Rogazzle]

And here we are about 12 weeks in with finasteride.

Shedding really picked up after the 2nd month mark from 40 or so hairs a day to 60 - 80. Still shedding about 40 - 60 hairs a day, it appears to be slowing. Notably most of the hairs shed are the point-tipped miniaturization type hairs which are 2" - 3" long (I wonder if these are minoxidil hairs). My mature terminal hairs are about 4" - 6" long.

Either way I have a storm of regrowth happening at the crown. There are hundreds of hairs coming in and outpacing the shedding itself.

These pictures where taken after parting the hair and fluffing up the regrowth along the part line using a comb.

Edit: A comparison pic from March 2011

Crown pic for hair length reference, not meant for density reference since I do not have a comparison.

At this rate things should be getting interesting in the months ahead. These new hairs will definitely improve my crown density.

Regimen notes:

Been off the miconazole since starting finasteride.

Only minoxidil once a day at the crown.

Finasteride now at 1mg day.

No longer using Tricomin. Stopped after 7 weeks (ran out) may continue again later. Still attribute the regrowth to finasteride.

No internal supplements.

No sides.

 

[chore boy]

I hate to employ counter-trolling measures but you're just mouthy for no reason. It's not witty humor, trust me... it just makes you look ridiculous.

I wanna say I read that you're something like 36 years old. Speaking to board members the way you do and using words like "LULZ" and "ownage" only corroborates my beliefs that you're just a little boy mentally and wouldn't dare pop off on folks, in person, the way you do online. Give it up, homey.

And for the record, those crusty bats you posted pictures of are far from cougars... caked up mascara and whatnot... hahaha

I kinda wish I was handling your CB on that group buy... I'd cut and stomp that shyt worse than a Memphis dope house.

 

[Rogazzle]

^^^ Yeah my thoughts exactly with ordering compounds from unknown strangers.

Luckily, finasteride seems to be working miracles.

BTW, did I tell you, I have zero sides? How was your panic attack you had this morning?

 

[thinninghairsucks]

hahahaha

haven't been here in a while and roggazle is still up to his old tricks...

your hair is actually looking much better now your off the mico and on the minoxidil and finasteride

at least we now know that mico did nothing for your hair but minoxidil did

interesting... this gives me hope for bimaprost or whatever that eyelash sh*t is called. I cant be bothered looking it up, you know what i mean though

finasteride in combo with minoxidil is clearly helping your hair a little bit.... nothing crazy, but definitely a physical and noticeable change so good on you..

whether you have had no sides is something that we cant prove and will have to take your word on

sadly there are far to many horror stories and people getting limited results for me to ever jump on it. My dick is more important then my hair.

on a side note. your a total arsehole

 

[Rogazzle]

Wassup everybody. I wanna see report cards.

Any updates?

 

[Rogazzle]

hahahaha

haven't been here in a while and roggazle is still up to his old tricks...

your hair is actually looking much better now your off the mico and on the minoxidil and finasteride

at least we now know that mico did nothing for your hair but minoxidil did

interesting... this gives me hope for bimaprost or whatever that eyelash sh*t is called. I cant be bothered looking it up, you know what i mean though

finasteride in combo with minoxidil is clearly helping your hair a little bit.... nothing crazy, but definitely a physical and noticeable change so good on you..

whether you have had no sides is something that we cant prove and will have to take your word on

sadly there are far to many horror stories and people getting limited results for me to ever jump on it. My dick is more important then my hair.

^^^

Still no sides, in fact, I've upped my finasteride to 2mg/day for the past 4 weeks, why? becuz, I can. Now settling back into 1mg.

After 6 months my overall crown density is up 30+%.

Booya!

on a side note. your a total arsehole

Thanx! I also like to beat off on rainy days. and then take a little nap.

 

[Rogazzle]

And here we are now with 21 weeks (5 months) on finasteride.

With flash

No flash

For the past 4 weeks I've upped the dose from .5mg day to 2mg. I am still completely sides free.

Today I drop it down to 1mg and will stick with it from here on out.

I can't wait to see my 1 y.r. results. 7 more months to go!

Groow. Grooow!!!

 

[Rogazzle]

oops yeh, it's Oct 20 not 21.

But wutever.

 

[guy83]

i love your avatar made me realize that i dont chew my food long enough .

 

[squeegee]

Econazole and miconazole inhibit steroidogenesis and disrupt steroidogenic acute regulatory (StAR) protein expression post-transcriptionally.
Walsh LP, Kuratko CN, Stocco DM.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Abstract
The imidazole antifungal drugs econazole and miconazole have previously been shown to disrupt steroidogenesis in Leydig and adrenal cells by inhibiting 17alpha-hydroxylase/17,20-lyase (P450c17) enzyme activity, thus reducing the conversion of progesterone to androstenedione. However, a recent study in Y-1 adrenal cells indicated that these compounds may also reduce the availability of cholesterol to the cytochrome P450 side chain cleavage (P450(scc)) enzyme, the first enzyme in the steroidogenic pathway. Since the steroidogenic acute regulatory protein (StAR) mediates the transfer of cholesterol from the outer to the inner mitochondrial membrane where the P450(scc) enzyme resides, an action which constitutes the rate-limiting and acutely-regulated step in steroidogenesis, we hypothesized that these drugs may also reduce StAR expression and/or activity. Our studies demonstrate that these drugs reversibly inhibited (Bu)(2)cAMP-stimulated progesterone production in a dose- and time-dependent manner in MA-10 cells without affecting total protein synthesis or P450(scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme expression or activity. In contrast, they dramatically decreased (Bu)(2)cAMP-stimulated StAR protein expression post-transcriptionally. This study indicates that StAR protein is susceptible to inhibition by at least some imidazole compounds that inhibit steroidogenesis.

PMID: 11282276 [PubMed - indexed for MEDLINE


Higher Levels of Steroidogenic Acute Regulatory Protein and Type I 3bold italic beta-Hydroxysteroid Dehydrogenase in the Scalp of Men with Androgenetic Alopecia
http://www.nature.com/jid/journal/v126/ ... 0442a.html

 

[squeegee]

Hairloss Study Abstract: The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.

Title
The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.
Author
Albertson BD; Frederick KL; Maronian NC; Feuillan P; Schorer S; Dunn JF; Loriaux DL
Address
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland 20892.
Source
Res Commun Chem Pathol Pharmacol, 61: 1, 1988 Jul, 17-26
Abstract
The in vitro inhibition of Leydig cell microsomal steroidogenesis by ketoconazole, a potent P-450 dependent enzyme blocker, was evaluated in the human, stallion and pig. Purified Leydig cells were isolated by mechanical dispersion of teased, decapsulated whole testes and sieving through a 0.25 mm stainless steel mesh. The activity of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase), 17,20-desmolase (17,20D), 17-ketosteroid reductase (17-KSR) and aromatase were measured using a constant amount (50 microM) of 14C-labelled substrates in the presence of varying concentrations of pure ketoconazole. Products were isolated by thin layer chromatography and verified by derivative formation. 17-OHase and 17,20D activities were significantly inhibited (p less than .001) by ketoconazole at concentrations as low as 5 microM. 3 beta-HSD, 17-KSR and aromatase activities were only significantly inhibited by ketoconazole at concentrations of 500 and 5000 microM. These data describe the specific loci of inhibition of ketoconazole on testicular steroidogenesis and confirm the observations that ketoconazole is an effective inhibitor of androgen biosynthesis in several species.
Language of Publication
English
Unique Identifier
89018625



http://en.wikipedia.org/wiki/File:Steroidogenesis.svg

 

[squeegee]

Human Skin is a Steroidogenic Tissue: Steroidogenic Enzymes and Cofactors Are Expressed in Epidermis, Normal Sebocytes, and an Immortalized Sebocyte Cell Line (SEB-1)

Although the human sebaceous gland can synthesize cholesterol from acetate and can further metabolize steroids such as dehydroepiandrosterone into potent androgens, the de novo production of steroids from cholesterol has not been demonstrated in human skin. The goal of this study was to delineate the steroidogenic pathway upstream from dehydroepiandrosterone by documenting the presence of members of the P450 side chain cleavage system (P450scc). This system catalyzes the initial step in steroid hormone synthesis following translocation of cholesterol to the inner mitochondrial membrane. In concert with its cofactors, adrenodoxin and adrenodoxin reductase, and the transcription factor steroidogenic factor 1, P450scc converts cholesterol to pregnenolone. An SV40 immortalized human sebaceous gland cell line (SEB-1) was established in order to facilitate investigation of the P450scc system. The sebaceous phenotype of SEB-1 sebocytes was confirmed using immunohistochemistry, Oil Red O staining, and gene array expression analysis. Presence of P450scc, adrenodoxin reductase, cytochrome P450 17-hydroxylase (P450c17), and steroidogenic factor 1 was documented in human facial skin, human sebocytes, and SEB-1 sebocytes. Using immunohistochemistry, antibodies to the above proteins localized to epidermis, hair follicles, sebaceous ducts, and sebaceous glands in sections of facial skin. Results of immunohistochemistry were confirmed with Western blotting. Biochemical activity of cytochrome P450scc and P450c17 was demonstrated in SEB-1 sebocytes using radioimmunoassay. The relative abundance of mRNA for P450scc, P450c17, and steroidogenic factor 1 in SEB-1 sebocytes and sebaceous glands was compared to mRNA levels in ovarian theca and granulosa cells using real-time quantitative polymerase chain reaction. Gene array expression analysis and quantitative polymerase chain reaction indicated that mRNA for P450scc is more abundant than mRNA for both P450c17 and steroidogenic factor 1 in sebaceous glands and SEB-1 cells. These data demonstrate that the skin is in fact a steroidogenic tissue. The clinical significance of this finding in mediating androgenic skin disorders such as acne, hirsutism, or androgenetic alopecia remains to be established.

http://www.nature.com/jid/journal/v120/ ... 3399a.html

 

[squeegee]

And a knuckle hair update for NES.

hahahahahaha!! unk: unk: unk: unk:

This sh*t is funny !!

 

[squeegee]

Hey Rog! Are you using a generic brand for your 4% Miconazole? How big is the tube 30-45 grams.. Cannot find it anywhere... The last batch that I got was from Ebay.. The product is not manufactured anymore.. 4% is the real sh*t... I got the same results just like you..Keep this thread alive!! Bad ***!!! unk:

viewtopic.php?t=57738&f=23

 

[whymelord]

You can still buy monistat online, which is 4%, but is this somehow less desirable? I wish I could find a 4% cream that was mineral oil-free. The monistat also seems to come in "3 day" packages...

 

[squeegee]

Thank you WhymeLord!! I will check into this!

Steroidogenesis

Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. The pathways of steroidogenesis differ between different species, but the pathways of human steroidogenesis are shown in the figure.

Products of steroidogenesis include:

androgens
testosterone
estrogens and progesterone
corticoids
cortisol
aldosterone

Steroids include estrogen, cortisol, progesterone, and testosterone. Estrogen and progesterone are made primarily in the ovary and in the placenta during pregnancy, and testosterone in the testes. Testosterone is also converted into estrogen to regulate the supply of each, in the bodies of both females and males. Certain neurons and glia in the central nervous system (CNS) express the enzymes that are required for the local synthesis of pregnane neurosteroids, either de novo or from peripherally-derived sources. The rate-limiting step of steroid synthesis is the conversion of cholesterol to pregnenolone, which occurs inside the mitochondrion.[10]

 

[squeegee]

Steroidogenic isoenzymes in human hair and their potential role in androgenetic alopecia.
Hoffmann R.
Source

Department of Dermatology, Philipp University, Marburg, Germany.
Abstract

Androgenetic alopecia (Androgenetic Alopecia) is the most common type of hair loss. The relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait, and a polygenic basis is considered to be most likely. So far, the predisposing genes for Androgenetic Alopecia are unknown and we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss, but Androgenetic Alopecia can be defined as a dihydrotestosterone (DHT)-dependent process with continuous miniaturization of sensitive hair follicles. The type 2 5alpha-reductase plays a central role by the intrafollicular conversion of testosterone to DHT. However, due to the increasing knowledge in this field, we now know that there are many more steroidogenic enzymes involved in the onset and development of Androgenetic Alopecia, and this article shall provide a critical overview of recent discoveries.

Copyright 2003 S. Karger AG, Basel

 

[squeegee]

Enzymology of the hair follicle

European Journal of Dermatology. Volume 11, Number 4, 296-300, July - August 2001, Articles de la revue


Summary

Author(s) : R. Hoffmann, Department of Dermatology, Philipps-Universität, Deutschhausstraße 9, D-35033 Marburg, Germany..

Summary : Androgenetic alopecia (Androgenetic Alopecia) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. A genetic predisposition is a feature of Androgenetic Alopecia, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far move advanced, and human hair follicles are not only targets for androgens, but also reveal an active androgen metabolism, with the ability to convert several androgens by different steroidogenic enzymes. Recent results suggest that the dermal papilla of the hair follicle expresses abundant type 2 5a-reductase, 3b-HSD and steroid sulfatase activity. Therefore, current information about the androgen metabolism in hair follicles is reviewed and the potential impact on future therapeutic approaches is discussed.

Keywords : hair, hair loss, androgens, androgen metabolism.

Pictures

ARTICLE

Androgenetic alopecia (Androgenetic Alopecia) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. Although clinically different, the pathogenetic pathways leading to this type of hair loss are thought to be similar in both sexes [1]. A genetic predisposition is a feature of Androgenetic Alopecia, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far more advanced, and with this article the present knowledge of steroidogenic isoenzymes within the human hair follicle and their role in the pathogenesis of Androgenetic Alopecia will be reviewed.
Androgen metabolism and hair growth

Androgens are required in males for the development of normal genitalia in utero, and with the beginning of puberty they become necessary for the libido and secondary sexual characteristics as well as for maturation and growth of the male muscle mass. Moreover, they are involved in the pathogenesis of hair disorders such as hirsutism and Androgenetic Alopecia. More than 50 years ago Hamilton observed that men who were castrated did not develop Androgenetic Alopecia [2]. Therefore it was concluded that the growth of hair follicles is in some parts of the body androgen-dependent (Table I). At present it is unknown how androgens exert their paradoxical effect on the growth of HF in different body sites, and which genes are involved. However, Hamilton already showed that Androgenetic Alopecia can be triggered in castrated men by injecting testosterone.

The synthesis of androgens is complex because it occurs in several organs, each of which has its own pecularities. The androgen metabolism (AM) of adrenals and gonads and the influence of the pituitary gland are beyond the scope of this review and are described in detail elsewere [3].

The pathway of androgens begins with cholesterol which is converted to pregnenolone. Following alpha-hydroxylation at the C17-position, the action of the enzyme C17-20 lyase cleaves distal carbon moities, leaving a C 19 carbon steroid with a C-17 ketone in the distal ring. These "17-ketosteroids" make up a group of relatively weak androgens, such as dehydroepiandrosterone (DHEA), defined by their relatively low affinity to the androgen receptor (AR). Approximately 75% of DHEA and 95% of DHEA-S is derived from the adrenal gland. These weak androgens, however, can be enzymatically converted to more potent androgens such as T which is the major circulating androgen. In the HF the principal pathways involved in conversion of weak to more potent androgens are through activity of the enzymes 3beta-hydroxysteroid dehydrogenase/delta5=>4-isomerase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). In most target organs T can be further metabolized to DHT via the action of 5alpha-reductases 5alpha-R (Fig. 1). The affinity of DHT to the AR is approx. five-fold higher than that of T. Potent androgens such as T or DHT can be removed by conversion to weaker androgens, or they can be metabolized via the aromatase to estrogens, or they can be glucuronidated to form androgen conjugates that are more rapidly cleared from the circulation. Remarkably, some target tissues show enhanced AM and androgen sensitivity [3]. Circulating DHEA-S may be more rapidly metabolized to DHEA via steroid sulfatase (STS), DHEA would be, in turn, more rapidly converted to androstenedione if increased 3beta-HSD activity is present. Androstenedione would be converted to T if 17beta-HSD activity is present. If target cells convert weak androgens at an accelerated pace, then there will be enhanced conversion of T to DHT. Another reason for the increased sensitivity of a target to androgens is believed to be an increase in the number of AR.

Only a small fraction of androgens exist as free steroids in the circulation, with an equilibrium between free androgen hormone and protein-bound androgens. The most important protein for androgen binding is the sex-hormone binding globulin (SHBG). Normally approx. 70% of T is bound to SHBG, 19% to albumin and only the remainder is unbound. Whether the bound fractions are still metabolically active is a matter of controversy, but the binding of androgens to SHBG is an important factor of AM because it acts somehow as a "sink" for circulating T.

To sum up, the AM is highly complex and can be tuned at various points, e.g. the amount of weak androgens present for conversion to more potent androgens, the repertoire of metabolizing enzymes present in target cells, the ratio of conversion and reconversion, the concentration of SHBG in the serum, the affinity of androgens to the AR.

The principal elements of the androgen metabolism can be summarized as follows:

Androgen-dependent processes are not the result of the summation of the activity of individual metabolites, but are solely due to the binding of DHT and translocation of the receptor to the nucleus. This concept has been discussed for the development of benign prostate hyperplasia [4], and is most likely valid for Androgenetic Alopecia as well. Therefore DHT-dependent cell functions will only be initiated or will be amplified if:

i: enough weak androgens are present for conversion;

ii: more potent androgens are formed via the action of 5alpha-R;

iii: the enzymatic activity of androgen inactivating enzymes is rather low: e.g. aromatase;

iv: reconversion of weaker steroids to DHT takes place;

v: functionally active AR are present in high numbers.
Steroidogenic enzymes within the hair follicle

Steroid sulfatase (STS)

The skin is capable of synthesizing active androgens, such as DHT, from the systemic precursor DHEA-S. The first step in this route is the desulfatation of DHEA-S by the enzyme steroid sulfatase (STS). Because DHEA is further metabolized to androstendione, T and in the hair follicle (HF) to DHT [5], STS is an important enzyme for the conversion of the weak adrenal androgens to more potent androgens in the periphery. DHEA-S is believed to maintain axillary hair and is thought to be involved in the pathogenesis of hirsutism [6] in women. In women, however, excess of DHEA-S or the STS metabolite is believed to be involved in several androgen-dependent processes such as acne and Androgenetic Alopecia [40]. Remarkably, DHEA-S and DHEA plasma levels seem to correlate with balding in young men [42] indicating that STS may play a role in the pathogenesis of Androgenetic Alopecia, and recently we were able to show that the dermal papilla (DP) is the predominant site of STS expression, and that STS can be inhibited by estrone sulfamate [5]. Therefore STS within the human hair follicle appears to be an interesting pharmaceutical target to treat Androgenetic Alopecia or hirsutism.

3beta-hydroxysteroid dehydrogenase/delta5 => 4-isomerase (3beta-HSD)

The 3beta-HSD isoenzymes catalyze an obligatory step in the biosynthesis of androgens, estrogens, mineralocorticoids and glucocorticoids. The two 3beta-HSD isoforms are expressed in a tissue-specific manner involving separate mechanisms of regulation. The structures of several cDNAs encoding 3beta-HSD isoenzymes have been characterized in human and several other vertebrate species.

The importance of the 3beta-HSD in male steroid hormone physiology is underscored by a genetically determined deficiency that is transmitted as an autosomal recessive trait and is characterized by varying degrees of salt wasting. All mutations were detected in the type II 3beta-HSD gene, which is expressed almost exclusively in the adrenals and gonads. No mutation was detected in the type I 3beta-HSD gene, which is believed to be expressed in peripheral tissues. Whether hair growth is affected in these individuals has not been investigated so far, but because of the importance of 3beta-HSD in the AM and increased activity in Androgenetic Alopecia [11], this question warrants further investigation. Today we know that 3beta-HSD activity is present in hair follicles and sebaceous glands because homogenates of the isolated sebaceous glands (ex vivo) exhibited 17beta-HSD and 5alphaR activities as well as high 3beta-HSD/D5 => 4-i activity, which was highest in the sebaceous glands isolated from HF affected by Androgenetic Alopecia [11]. Immunohistochemical studies confirmed these results showing that 3beta-HSD/D5 =>4-i is located in the sebaceous gland and only the type 1 3beta-HSD/D5 =>4-i is believed to be present in the skin [12]. However, plucked HF (without sebaceous gland) ex vivo also exhibit marked 3beta-HSD/D5 =>4-i activity [22] and detectable mRNA in outer root sheath keratinocytes [15]. We were able to show that in contrast to the ORS and CTS, the DP exclusively metabolizes androstendiol to T, thus indicating 3beta-HSD activity. Which kind of HF cells express a specific type of 3beta-HSD/D5 =>4-i isoenzyme is unknown.

17beta-hydroxysteroid dehydrogenases (17beta-HSD)

Isoenzymes of 17beta-HSD regulate levels of bioactive androgens and estrogens in a variety of tissues. At present five isoenzymes of 17beta-HSD that differ in tissue expression and requirements of cofactors such as NADPH for type III 17beta-HSD, and NAD(+) for type 2 17beta-HSD are known (Table III). The importance of the type 3 enzyme in male steroid hormone physiology is underscored by the genetic disease 17beta-HSD deficiency. Mutations in the type 3 17beta-HSD gene impair the formation of testosterone in the fetal testis and give rise to genetic males with normal male Wolffian duct structures but female external genitalia very similar to the abnormalities seen in 5alpha-R deficiency. These individuals are usually brought up as females, but at puberty there is a striking rise in testosterone levels and they change their social sex. To date, more than 18 recessive mutations have been identified, giving rise to different clinical phenotypes. The potential significance of 17beta-HSD isoenzymes in Androgenetic Alopecia is underscored by the observations of Hodgins et al. [16] who plucked hair follicles from young adults not yet expressing Androgenetic Alopecia but with a strong family history of baldness, and found two populations, one with high 17beta-HSD activity and one with low enzyme activity. This study suggests that low enzyme activity may be related to lesser degrees of balding. Therefore, linkage of the genes coding for the 17beta-HSD isoenzymes and Androgenetic Alopecia warrants further investigations.

Very early on it was shown that plucked human HF or HF from the stump-tailed macaques express considerable 17beta-HSD activity due to the principle metabolite of T being androstenedione (Fig. 1). The isoenzyme-specific expression pattern in different parts of the HF has so far not been investigated in detail mainly because of technical problems. Only one study describes the type 1 and 2 17beta-HSD in the epithelial parts of the HF [15]. These results are in line with our studies where we were able to show that in contrast to the CTS and RS the DP exhibits only little 17betaHSD activity [17].
5alpha-reductases (5alpha-R)

The microsomal enzyme steroid 5alpha-R is responsible for the conversion of testosterone into the more potent androgen DHT and the conversion of androstenedione to 5alpha-androstanedione (Fig. 1). 5a-R deficiency is a rare autosomal recessive trait that was first described by Nowakowski and Lenz [18], although, without etiological characterization which was not possible at that time. In 1974 it became clear that these individuals lack functional 5alpha-R [19] and today we know that the type 2 5alpha-R is lacking [55]. In typical cases, a 46, XY male who has testes, normal plasma T and low DHT levels is observed. Interestingly, no or minimal beard growth or Androgenetic Alopecia is seen in these men. These observations together with the finding that both humans and stump-tailed macaques have beard and frontal scalp HF with higher 5alpha-R activity than HF from the occiput [23, 24] indicates that the type 2 5alpha-R is crucially involved in the pathogenesis of androgen-dependent hair growth and that the inhibition of this isoenzyme is therefore a rational approach for treatment.

Today two distinct isoforms designated type 1 and type 2 have been cloned. Subsequently it has been shown that both isoenzymes have distinct molecular, biochemical and tissue expression characteristics (Table IV). In humans, mutations in the gene coding for the type 1 5alpha-R have not been reported. In mice, however, a mutation in this gene will cause early fetal death because of estrogen excess in utero.

Early studies have revealed that plucked human hair follicles (HF) are able to convert testosterone (T) to the more potent androgen dihydrotestosterone (DHT) via the action of the enzyme 5alpha-R [27]. Recently, the presence of both type 1 and type 2 5alpha-R within human HF has been demonstrated [25], but the intrafollicular localization of both isoenzymes remains controversial. Special attention has been paid to the DP and several authors have tried to localize both isoenzymes within the DP. So far, for the examination of the androgen metabolism in the hair follicle, cultivated primary cell lines of papilla cells [26-29], keratinocytes, and dermal reticular fibroblasts [30] have been used. Some authors were unable to find considerable 5alpha-R activity in occipital scalp DP [47, 48, 50], whereas others found this enzyme in beard and occipital scalp DP [32, 33]. Recently we were able to show that the main metabolic activity of type 2 5alpha-R can be detected in intact occipital scalp and beard DP [34]. These results are in contrast to the above mentioned results measuring the testosterone consumption in DP cell cultures, but are in line with the observation of type 2 5alpha-R activity below the HF isthmus [35] and with the detection of type 2 5alpha-R mRNA in DP cells [15].

Aromatase

The cytochrome P450 aromatase (P450arom) enzyme is required for bioconversion of androgens to estrogens. Only a single human gene encoding P450arom (CYP19) has been isolated. Mutations in the CYP19 gene do occur occasionally and result in aromatase deficiency. Girls show pseudohermaphrodism at birth which is sometimes corrected by surgical repair of the external genitalia, including a clitoridectomy. Males are rather tall with eunuchoid skeletal proportions. Their bone age is retarded and osteopenia can be observed, indicating that estrogens are crucially important for bone development. At puberty females will develop hirsutism due to an androgen excess and in theory females and males might develop early onset Androgenetic Alopecia. However, this question has not been investigated so far. Localizing the aromatase in the external root sheath of anagen HF suggests that aromatase may have a function in the intrafollicular AM by converting potent androgens to less potent estrogens in order to avoid potentially harmful androgen-mediated effects on androgen-dependent HF. This concept is supported by the fact that women taking aromatase inhibitors for the treatment of breast cancer will often experience Androgenetic Alopecia-like hair loss. Moreover, in both men and women aromatase activity has been shown to be diminished in HF affected by Androgenetic Alopecia [24].

CONCLUSION

Summary and future perspectives

Androgenetic Alopecia can be defined as a DHT-dependent process with continuous miniaturization of sensitive HF. So far the predisposing genes for Androgenetic Alopecia are unknown and we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss. However, the local AM plays a central role in the intrafollicular conversion of weak androgens such as DHEAS to more potent androgens such as T or DHT. Within the HF the DP plays a central role by exhibiting an array of important steroidogenic isoenzymes. Provided that the DP cell triggers and regulates the growth of HF, this physiological role may be reflected by metabolic differences which could account for differences in androgen sensitivity as observed in HF from different body sites, and in conditions such as male pattern baldness. The observation of STS, 3betaHSD and type 2 5alpha-R-activity within the DP could be a clue in the understanding of the regulation of androgen action in the human hair follicle by local androgen modification at the target cell level. Therefore, in the future some of the intrafollicular steroidogenic enzymes are potential pharmaceutical targets for the treatment of Androgenetic Alopecia or hirsutism.