Androgenetic Alopecia Comparative Study- Gene Expression Differences

[sktboiboi]

Dude are you serious? Why do you think I still know every single post in this thread which is years old? I was part of the thread and I was one of the dozens of users and Progesterone didn't do sh*t for anyone. I was using it 10 months or so and my hair was worse after these 10 months. And that was the same for the other testers. I don't care if you believe me or not. Waste your time if you want. But now you have the information. Do with these information whatever you want.

i back up everything here with studies- n its only 4 pages long

you back up yours with an entire thread (20overpages) of bro science that u expect me to read. Also, after reading the last few pages, i cant find even a single post that indicated that's p4 is not working for them.

I am requesting u to refrain from posting comments in this thread if u cant backup what u've said with verifiable studies- broscience excluded.

Thanks.

 

[FCKW36]

Studies won't bring you hair. That's the reality. And the reality is that Progesterone won't bring you a single hair. You can believe what you want and feel free to test it but I only can tell you that you are not the first one. Good luck.

 

[sktboiboi]

Studies won't bring you hair. That's the reality.

and bro science like what u're advocating would?

And the reality is that Progesterone won't bring you a single hair. You can believe what you want and feel free to test it but I only can tell you that you are not the first one. Good luck.

while bro science from self-made professors in trichology like u would?

Thanks

 

[FCKW36]

Call it Bro science as often as you want but I call it experience and you will make your own soon. Good luck.

 

[abcdefg]

and bro science like what u're advocating would?

while bro science from self-made professors in trichology like u would?

Thanks

What do you think of propecia long term? Are you on that too?

 

[sktboiboi]

Call it Bro science as often as you want but I call it experience and you will make your own soon. Good luck.

thanks then i would rather not listen to the 'experiences' of individuals and instead, logically, entrust my faith into studies on Androgenetic Alopecia.

Thanks.

I repeat: pls refrain from posting in this thread if u do not have verifable studies to backup what u've said- https://www.urbandictionary.com/define.php?term=broscience excluded. I wanna keep the thread short, clean and informative.

 

[Murkey Thumb]

thanks then i would rather not listen to the 'experience' of individuals and instead, logically entrust my faith into studies on Androgenetic Alopecia.

Thanks.

I repeat: pls refrain from posting in this thread if u do not have verifable studies to backup what u've said- https://www.urbandictionary.com/define.php?term=broscience excluded. I wanna keep the thread short, clean and informative.

I think you are wrong we need to share our experiences as much as possible. The causes of hair loss are multiple, not singular what works for one may not work for another, studies verified or not. Zix works for people, cet works for others no studies.

 

[sktboiboi]

I think you are wrong we need to share our experiences as much as possible. The causes of hair loss are multiple, not singular what works for one may not work for another, studies verified or not. Zix works for people, cet works for others no studies.

that's not what this thread is for.

The tittle of it says it all.

Again, i made this thread for discussions on Androgenetic Alopecia studies- not bro science anecdotes. U already nailed it home- somethings might work on some people, while other stuff might not. some people might have Androgenetic Alopecia due to misregulation of pathways X, while others might be affected by others like pathway Y.

The causes of hair loss are multiple, not singular

there u go again, u are of no difference with the majority here. for you're like declaring:

'The sky is blue, but we dont know why it's blue'

Question is:

like what?

the answer to the question above is precisely the reason that i made this thread to dive deeper into the multiple causes of Androgenetic Alopecia and based on the data from the studies- the possible solutions to address them.

Please refrain from commenting if u dont have studies to backup them that ALL can peruse and debate about- bro science excluded.

Thanks.






*how's the explosive diarrhea and choked arteries going from the 1ml castor oil orally? Wait, u aint getting them?? guess my system was already screwed then.

 

[sktboiboi]

ok further on Progesterone.

From the gene differences comparision study at http://sci-hub.tw/https://doi.org/10.1111/jdv.14278 at page 10, it listed the following pathways downregulated in Androgenetic Alopecia tissues:

Hedgehog signaling pathway
Progesterone-mediated oocyte maturation
Oocyte meiosis
SNARE interactions in vesicular transport
Phospholipase D signaling pathway
Maturity onset diabetes of the young
Synthesis and degradation of ketone bodies
Transcriptional misregulation in cancer
Basal cell carcinoma
Pathways in cancer

I have talked about the'Progesterone-mediated oocyte maturation' pathway, whose description was:

Xenopus oocytes are naturally arrested at G2 of meiosis I. Exposure to either insulin/IGF-1 or the steroid hormone progesterone breaks this arrest and induces resumption of the two meiotic division cycles and maturation of the oocyte into a mature, fertilizable egg. This process is termed oocyte maturation. The transition is accompanied by an increase in maturation promoting factor (MPF or Cdc2/cyclin B) which precedes germinal vesicle breakdown (GVBD). Most reports point towards the Mos-MEK1-ERK2 pathway [where ERK is an extracellular signal-related protein kinase, MEK is a MAPK/ERK kinase and Mos is a p42(MAPK) activator] and the polo-like kinase/CDC25 pathway as responsible for the activation of MPF in meiosis, most likely triggered by a decrease in cAMP.




Now lets look at the 'Oocyte meiosis' pathway.






From its description at http://www.genome.jp/kegg-bin/show_pathway?hsa04114+5604 :

"During meiosis, a single round of DNA replication is followed by two rounds of chromosome segregation, called meiosis I and meiosis II. At meiosis I, homologous chromosomes recombine and then segregate to opposite poles, while the sister chromatids segregate from each other at meoisis II. In vertebrates, immature oocytes are arrested at the PI (prophase of meiosis I). The resumption of meiosis is stimulated by progesterone, which carries the oocyte through two consecutive M-phases (MI and MII) to a second arrest at MII. The key activity driving meiotic progression is the MPF (maturation-promoting factor), a heterodimer of CDC2 (cell division cycle 2 kinase) and cyclin B. In PI-arrested oocytes, MPF is initially inactive and is activated by the dual-specificity CDC25C phosphatase as the result of new synthesis of Mos induced by progesterone. MPF activation mediates the transition from the PI arrest to MI. The subsequent decrease in MPF levels, required to exit from MI into interkinesis, is induced by a negative feedback loop, where CDC2 brings about the activation of the APC (anaphase-promoting complex), which mediates destruction of cyclin B. Re-activation of MPF for MII requires re-accumulation of high levels of cyclin B as well as the inactivation of the APC by newly synthesized Emi2 and other components of the CSF (cytostatic factor), such as cyclin E or high levels of Mos. CSF antagonizes the ubiquitin ligase activity of the APC, preventing cyclin B destruction and meiotic exit until fertilization occurs. Fertilization triggers a transient increase in cytosolic free Ca2+, which leads to CSF inactivation and cyclin B destruction through the APC. Then eggs are released from MII into the first embryonic cell cycle."


= Progesterone upregulates this pathway- along with the 'Progesterone-mediated oocyte maturation' pathway

 

[sktboiboi]

so it is a widely-circulated myth that bald men are more virile.

However, it has been discovered that it is in fact the opposite.

http://www.dailymail.co.uk/health/a...-hair-30-lower-sperm-count-study-reveals.html

Bald men aren't as fertile as you think: Men who lose their hair at 30 have a lower sperm count, study reveals

• Sperm volume count was nearly 60 per cent lower in men who lost hair
• Hormonal changes associated with hair loss may adversely affect semen
• One in seven couples - or 3.5million people - have difficulty conceiving

By Roger Dobson for The Mail on Sunday

PUBLISHED: 22:05 BST, 12 September 2015 | UPDATED: 00:52 BST, 13 September 2015

• e-mail
  

2.8kshares
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Hairless: Bruce Willis is the epitome of an all-action man - but a study shows those who lost their hair at 30 may in fact be less fertile

Folklore may have it that baldness is a sign of a man’s virility, but a new study shows that those who lose their hair while young – at about 30 – may in fact be less fertile.

Sperm volume count was nearly 60 per cent lower in men with moderate to severe hair loss, and the researchers say that hormonal changes associated with hair loss may also adversely affect semen.

So-called androgenetic alopecia, or male pattern baldness, is the most common form of hair loss in men and women.


It often progresses to baldness and affects about half of men over 50, but can start in their late teens.

In the new research, being reported in the journal Dermatologica Sinica, fertility specialists and dermatologists looked for links between semen quality and fertility.

Doctors carried out a series of tests on men with an average age of 31 and with normal to mild hair loss and moderate to severe hair loss.

They found that men with moderate to severe hair loss had significantly lower sperm counts than those in the normal to mild group. Volume was also down by about 20 per cent.



So what has baldness and sperm count got to do in hand?


in the study that stated Vit D is downregulated in Androgenetic Alopecia scalps, it also states these:

"Androgenetic Alopecia downregulated vs. controls (downregulated pathways in Androgenetic Alopecia tissue vs normal tissue)

Cytoskeleton
Cell adhesion
Keratin‐associated proteins
Subset of keratins
Connexins/cell communication
TGF‐β signalling pathway
Endopeptidase inhibitor activity
EGF‐like protein domain
Growth factor activity
Platelet activation
Spermatogenesis"



In the most severe forms of spermatogenic disorders, there is a condition called https://en.wikipedia.org/wiki/Azoospermia

'
Azoospermia

Semen analysis revealing no sperm cells and multiple white blood cells

Azoospermia is the medical condition of a man whose semen contains no sperm.'

so there is a family group of genes that scientists discovered to be missing(aka deleted) in the semen of men with Azoopermia- called the DAZ genes(DAZ = 'Deleted in Azoospermia')

https://www.ncbi.nlm.nih.gov/pubmed/9321470

The human DAZ genes, a putative male infertility factor on the Y chromosome, are highly polymorphic in the DAZ repeat regions.
Yen PH1, Chai NN, Salido EC.
Author information

Abstract
The DAZ genes on the human Y Chromosome (Chr) are strong candidates for the azoospermia factor AZF. They are frequently deleted in azoospermic or severely oligospermic males and are expressed exclusively in germ cells. In addition, the DAZ genes share a high degree of similarity with a Drosophila male infertility gene, boule. The predicted DAZ proteins contain an RNA recognition motif (RRM), and multiple copies of a repeat (the DAZ repeat) in tandem array. To understand the DAZ gene family and its expression, the DAZ genomic structure and RNA transcripts in numerous males, as well as several DAZ cDNA clones were analyzed. The results of genomic Southern blot showed that each male contains multiple DAZ genes with varying numbers of DAZ repeats, and that the copy number of the DAZ repeats are polymorphic in the population. The presence of multiple species of DAZ transcripts with different copy number and arrangement of the DAZ repeats in an individual suggests that more than one DAZ gene are transcribed. The existence of multiple functional DAZ genes complicates the analysis of genotype/phenotype correlations among males with varying sperm counts.


Another study also indicated that genes related to spermatogenesis are downregulated in Androgenetic Alopecia tissues:

https://patentimages.storage.googleapis.com/US20110021599A1/US20110021599A1-20110127-D00088.png

page 89- 7th, 8th and 9th genes- DAZ2, DAZ4


along with the first study in this thread that stated Hedgehog signalling is the most downregulated pathway in Androgenetic Alopecia tissues, there is another study on hedgehog signalling with spermatogenesis:

Hedgehog signalling promotes germ cell survival in the rat testis
Juho-Antti Mäkelä,1,5 Vuokko Saario,1 Sonia Bourguiba-Hachemi,1 Mirja Nurmio,1,2Kirsi Jahnukainen,3,4 Martti Parvinen,1 and Jorma Toppari1,2
Author information ► Article notes ► Copyright and License information ► Disclaimer
This article has been cited by other articles in PMC.

Go to:
Abstract
Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by a wide variety of germ cells. This suggests that Hh signalling is involved in spermatogenesis at many different levels. Our data show that canonical Hh signalling is turned off in early condensing spermatids that strongly express the negative regulator of the pathway, suppressor of fused (SUFU). Most of the Hh pathway specific mRNAs display the highest values in stages II–VI of the rat seminiferous epithelial cycle. The key endocrine regulator of germ cell differentiation, FSH, down-regulates Dhh mRNA levels in vitro. Hh signalling inhibition in vitro leads to massive apoptosis of germ cells. In prepubertal rat testis imatinib mesylate-induced inhibition of tyrosine kinases impinges on Dhh

 

[Spice_Lord]

Oops wrong thread, interesting studies.

Look up an article or two on the degeneration of the arrectus pili muscle in Androgentic Alopecia and let me know what you think.

 

[sktboiboi]

Oops wrong thread, interesting studies.

Look up an article or two on the degeneration of the arrectus pili muscle in Androgentic Alopecia and let me know what you think.

are u asking for my opinion on them?

based on what?

based on what article?

what do u mean by 'what i think' about them?

whats so hard to linking the '1 or 2' articles u're talking about(which i seriously dont)? especially when you're the 1 requesting for my opinion now?

 

[Armando Jose]

Here are some studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158628/
https://www.ncbi.nlm.nih.gov/pubmed/24579818
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500053/

discussion
https://www.hairlosstalk.com/interact/threads/arrector-pili-muscle-degeneration.80604/

 

[Spice_Lord]

Here are some studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158628/
https://www.ncbi.nlm.nih.gov/pubmed/24579818
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500053/

discussion
https://www.hairlosstalk.com/interact/threads/arrector-pili-muscle-degeneration.80604/

Thanks man lol, those are the studies I was actually talking about too. In my defense I accidently posted in this thread and I edited my post to be relevant to the thread, I was in a hurry and didn't have the links at the ready.

 

[sktboiboi]

Thanks man lol, those are the studies I was actually talking about too. In my defense I accidently posted in this thread and I edited my post to be relevant to the thread, I was in a hurry and didn't have the links at the ready.

part of the answer to your question on the loss of the Arretor pili muscle is here(pay attention to the underlined):

https://www.ncbi.nlm.nih.gov/pubmed/16049113

Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull.
Wada N1, Javidan Y, Nelson S, Carney TJ, Kelsh RN, Schilling TF.
Author information

Abstract
Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.







They may sound unrelated to you(arretor pili muscle), but based on the information i have accumulated in my head so far, they are.







https://www.ncbi.nlm.nih.gov/pubmed/8326155

Hair follicle proteoglycans.
Couchman JR1.
Author information

Abstract
Proteoglycans are polymorphic macromolecules present in all mammalian tissues, including the skin and its appendages. They consist of a core protein to which one or more glycosaminoglycan chains are covalently attached. Broadly, they can be divided into classes based on location and core protein structure. These classes include cell surface proteoglycans, basement membrane proteoglycans, small leucine-rich proteoglycans, large proteoglycans aggregating with hyaluronan, and intracellular granule proteoglycans. They have a wide range of functions, but little is known of the proteoglycans that are present in the epithelial and stromal compartments of hair follicles. However, the transmembrane proteoglycan syndecan may be important in follicle morphogenesis, both with respect to the epithelium and dermal papilla cells. Syndecan may possess both heparan and chondroitin sulfate chains, interacts with growth factors as well as fibronectin and interstitial collagens, and can associate in a transmembrane relationship with the cellular cytoskeleton. It is strongly expressed in mesenchymal cells coincident with stromal-epithelial interactions during tissue morphogenesis. Proteoglycans are present in all basement membranes, including those surrounding the epithelial compartment of hair follicles. Additionally, and quite unlike the dermis, the dermal papilla is enriched in basement-membrane components, especially a chondroitin 6-sulfate-containing proteoglycan, BM-CSPG. The function of this proteoglycan is not known, but developmental studies indicate that it may have a role in stabilizing basement membranes. In the hair cycle, BM-CSPG decreases through catagen and is virtually absent from the telogen papilla. One or more heparan sulfate proteoglycans, including perlecan, are also present in papilla and follicular basement membranes. Some of the leucine-rich proteoglycans, such as decorin, are associated with interstitial collagens, and may influence fibrillogenesis. Because small amounts of types I and III collagens may be present in anagen papillae, decorin may also be a constituent.

The hair bulb, is made of chondroitin-sulfate-rich protoglycans. If u were to check your shedded Androgenetic Alopecia-afflicted hairs individually and very closely, u almost always never see a hair bulb attached(or a drastically size-reduced one)








Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes.
Hino K1, Saito A2, Kido M1, Kanemoto S1, Asada R1, Takai T1, Cui M1, Cui X1, Imaizumi K3.
Author information

Abstract
The endoplasmic reticulum (ER) stress transducer, box B-binding factor 2 human homolog on chromosome 7 (BBF2H7), is a basic leucine zipper (bZIP) transmembrane transcription factor. This molecule is activated in response to ER stress during chondrogenesis. The activated BBF2H7 accelerates cartilage matrix protein secretion through the up-regulation of Sec23a, which is responsible for protein transport from the ER to the Golgi apparatus and is a target of BBF2H7. In the present study, we elucidated the mechanisms of the transcriptional activation of Bbf2h7 in chondrocytes. The transcription of Bbf2h7 is regulated by Sex determining region Y-related high-mobility group box 9 (Sox9), a critical factor for chondrocyte differentiation that facilitates the expression of one of the major cartilage matrix proteins Type II collagen (Col2), through binding to the Sox DNA-binding motif in the Bbf2h7 promoter. BBF2H7 is activated as a transcription factor in response to physiological ER stress caused by abundant synthesis of cartilage matrix proteins, and consequently regulates the secretion of cartilage matrix proteins. Taken together, our findings demonstrate novel regulatory mechanisms of Sox9 for controlling the secretion of cartilage matrix proteins through the activation of BBF2H7-Sec23a signaling during chondrogenesis.



https://www.ncbi.nlm.nih.gov/pubmed/18433381

SOX9 transduction increases chondroitin sulfate synthesis in cultured human articular chondrocytes without altering glycosyltransferase and sulfotransferase transcription.
Tew SR1, Pothacharoen P, Katopodi T, Hardingham Telogen Effluvium.
Author information

Abstract
The transcription factor SOX9 (Sry-type high-mobility-group box 9) is expressed in all chondrocytes and is essential for the expression of aggrecan, which during biosynthesis is substituted with more than 10 times its weight of CS (chondroitin sulfate) and is secreted by chondrocytes to form the characteristic GAG (glycosaminoglycan)-rich ECM (extracellular matrix) of cartilage. SOX9 expression rapidly falls during monolayer culture of isolated chondrocytes and this turns off aggrecan and associated CS synthesis. We therefore investigated whether SOX9 transduction of cultured human articular chondrocytes had any effect on the gene expression of the glycosyltransferases and sulfotransferases necessary for GAG biosynthesis. Retroviral SOX9 transduction of passaged chondrocytes increased the endogenous rate of GAG synthesis and the total capacity for GAG synthesis assessed in monolayer culture with beta-xyloside. Both the endogenous rate and the total capacity of GAG biosynthesis were increased further in chondrogenic cell aggregate cultures. The GAG synthesized was predominantly CS and the hydrodynamic size of the newly synthesized chains was unchanged by SOX9 transduction. Aggrecan gene expression was increased in the SOX9-transduced chondrocytes and increased further in chondrogenic culture, but no comparable effects were found in SOX9 transduced dermal fibroblasts. However, the expression of CS glycosyltransferase and sulfotransferase genes in chondrocytes was unaffected by SOX9 transduction. Therefore SOX9 transduction in chondrocytes increased their CS synthetic capacity, but this was not accompanied by changes in the transcription of the CS biosynthetic enzymes and must occur by indirect regulation of enzyme activity through control of enzyme protein translation or enzyme organization.

 

[sktboiboi]

https://www.ncbi.nlm.nih.gov/pubmed/20034104

Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage.
Park J1, Zhang JJ, Moro A, Kushida M, Wegner M, Kim PC.
Author information

Abstract
We report that Sonic Hedgehog (Shh) regulates both formation and patterning of tracheal cartilage by controlling the expression pattern and level of the chondrogenic gene, Sox9. In Shh(-/-) tracheo-esophageal tubes, Sox9 expression is transient and not restricted ventrally to the site of chondrogenesis, and is absent at the time of chondrogenesis, resulting in the failure of tracheal cartilage formation. Inhibition of Hedgehog signalling with cyclopamine in tracheal cultures prevents tracheal cartilage formation, while treatment of Shh(-/-) tracheal explant with exogenous Shh peptide rescues cartilage formation. Both exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh(-/-) tracheal culture, while promoting excessive cartilage development in wild-type trachea through induction of Sox9 expression. The ventral and segmented expression of Sox9 in tracheal primordia under Shh modulated by Bmp4 and Noggin thus determine where and when tracheal cartilage develops. These results indicate that Shh signalling is a critical determinant in tracheal cartilage development.


5th most upregulated gene in non-Androgenetic Alopecia scalp:

https://patentimages.storage.googleapis.com/US20110021599A1/US20110021599A1-20110127-D00088.png

https://www.genecards.org/cgi-bin/carddisp.pl?gene=COMP

Cartilage Oligomeric Matrix Protein


Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment.
Vidal VP1, Chaboissier MC, Lützkendorf S, Cotsarelis G, Mill P, Hui CC, Ortonne N, Ortonne JP, Schedl A.
Author information

Abstract
BACKGROUND:
The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development.

RESULTS:
Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge). Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man.

CONCLUSIONS:
We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment. Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.


From the gene differences comparision study at http://sci-hub.tw/https://doi.org/10.1111/jdv.14278 at page 10, it listed the following pathways as downregulated in Androgenetic Alopecia tissues:

Hedgehog signaling pathway
Progesterone-mediated oocyte maturation
Oocyte meiosis
SNARE interactions in vesicular transport
Phospholipase D signaling pathway
Maturity onset diabetes of the young
Synthesis and degradation of ketone bodies
Transcriptional misregulation in cancer
Basal cell carcinoma
Pathways in cancer

so the study said reduction of sox9, which is a downstream target gene of Hegdheog signalling = increases of GATA3 and etopic expression of it in parts of the hair follicle where it shouldn't even be expressed. so what is GATA3?:

https://www.researchgate.net/figure...A-3-is-induced-by-TCR-and-IL-4_fig4_263130756




= GATA3 is master regulator of Th2 cytokines and is:






GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells Umberto De Fanis,1 Francesca Mori,1 Rebecca J. Kurnat,1 Won Kyung Lee,1 Maria Bova,1 N. Franklin Adkinson,1 and Vincenzo Casolaro1 1Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell development and function. Consistently, studies in mice document their selective expression in Th1 and Th2 cells, respectively. In contrast, it is not clear whether these genes are regulated in human Th cells. Here we show that T-bet expression is polarized to a comparable degree in human and mouse Th-cell cultures, while only mouse GATA3 is subject to substantial regulation. This did not reflect differential skewing efficiency in human versus mouse cultures, as these contained similar frequencies of IFN-– and IL-4– producing cells. However, GATA-3 was expressed at significantly higher levels in human IL-4–producing cells enriched via capture with monoclonal antibodies (mAbs) against the PGD2 receptor, CRTH2, the best selective Th2-cell surface marker to date. Along with increased IL-4 and GATA-3, CRTH2 Th cells isolated from Th2-skewed cultures or the circulating memory pool exhibited markedly decreased IFN- and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to polarizing signals that are sufficient to direct Th2-specific expression in mouse cells. This postulates the involvement of an additional level of complexity in the regulation of human GATA-3 expression and stresses the existence of nontrivial differences in the regulation of human versus mouse T-cell function. (Blood. 2007;109:4343-4350)




= GATA3 ups Th2, which in turn ups PGD2 to up CRTH2




Prostaglandin D2 enhances lipid accumulation through suppression of lipolysis via DP2 (CRTH2) receptors in adipocytes.
Wakai E1, Aritake K2, Urade Y3, Fujimori K4.
Author information

Abstract
Prostaglandin (PG) D2 enhanced lipid accumulation in adipocytes. However, its molecular mechanism remains unclear. In this study, we investigated the regulatory mechanisms of PGD2-elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD2 receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD2-elevated intracellular triglyceride level. While, a DP2R agonist, 15R-15-methyl PGD2(15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level. In addition, the forskolin-mediated increase of cAMP-dependent protein kinase A (PKA) activity and phosphorylation of hormone-sensitive lipase (HSL) was repressed by the co-treatment with 15R. Moreover, the lipolysis was enhanced in the adipocyte-differentiated DP2R gene-knockout mouse embryonic fibroblasts. These results indicate that PGD2 suppressed the lipolysis by repression of the cAMP-PKA-HSL axis through DP2R in adipocytes.




=PGD2 ups lipid accumulation in adipocytes






Pronounced adipogenesis and increased insulin sensitivity caused by overproduction of prostaglandin D2 in vivo.
Fujitani Y1, Aritake K, Kanaoka Y, Goto T, Takahashi N, Fujimori K, Kawada T.
Author information

Abstract
Lipocalin-type prostaglandin (PG) D synthase is expressed in adipose tissues and involved in the regulation of glucose tolerance and atherosclerosis in type 2 diabetes. However, the physiological roles of PGD(2) in adipogenesis in vivo are not clear, as lipocalin-type prostaglandin D synthase can also act as a transporter for lipophilic molecules, such as retinoids. We generated transgenic (TG) mice overexpressing human hematopoietic PGDS (H-PGDS) and investigated the in vivo functions of PGD(2) in adipogenesis. PGD(2) production in white adipose tissue of H-PGDS TG mice was increased approximately seven-fold as compared with that in wild-type (WT) mice. With a high-fat diet, H-PGDS TG mice gained more body weight than WT mice. Serum leptin and insulin levels were increased in H-PGDS TG mice, and the triglyceride level was decreased by about 50% as compared with WT mice. Furthermore, in the white adipose tissue of H-PGDS TG mice, transcription levels of peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and lipoprotein lipase were increased approximately two-fold to five-fold as compared with those of WT mice. Finally, H-PGDS TG mice showed clear hypoglycemia after insulin clamp. These results indicate that TG mice overexpressing H-PGDS abundantly produced PGD(2) in adipose tissues, resulting in pronounced adipogenesis and increased insulin sensitivity. The present study provides the first evidence that PGD(2) participates in the differentiation of adipocytes and in insulin sensitivity in vivo, and the H-PGDS TG mice could constitute a novel model mouse for diabetes studies.

= PgD2 upregulation = hyper insulin-sensitivity and overexpressed adipogenesis(and sebocyte hyperprofileration. i have linked the studies about this b4 in this thread)

 

[sktboiboi]

so what has the PGD2 and adipogenesis(fat growth) got to do with arretor pili muscle?




Destruction of the arrector pili muscle and fat infiltration in androgenic alopecia.
Torkamani N1, Rufaut Norwood, Jones L, Sinclair R.
Author information

Abstract
BACKGROUND:
Androgenic alopecia (Androgenetic Alopecia) is the most common hair loss condition in men and women. Hair loss is caused by follicle miniaturization, which is largely irreversible beyond a certain degree of follicular regression. In contrast, hair loss in telogen effluvium (Telogen Effluvium) is readily reversible. The arrector pili muscle (APM) connects the follicle to the surrounding skin.

OBJECTIVES:
To compare histopathological features of the APM in Androgenetic Alopecia and Telogen Effluvium.

METHODS:
Archival blocks of 4-mm scalp punch biopsies from eight patients with Androgenetic Alopecia and five with Telogen Effluvium were obtained. New 4-mm biopsies from five normal cases were used as controls. Serial 7-μm sections were stained with a modified Masson's trichrome stain. 'Reconstruct' software was used to construct and evaluate three-dimensional images of the follicle and APM.

RESULTS:
The APM degenerated and was replaced by adipose tissue in all Androgenetic Alopecia specimens. Remnants of the APM remained attached to the hair follicle. There was no fat in the normal skin specimens. Fat was seen in two of five Telogen Effluvium specimens but could be attributed to these patients also showing evidence of Androgenetic Alopecia. Quantitative analysis showed that muscle volume decreased and fat volume increased significantly (P < 0·05) in Androgenetic Alopecia compared with controls.

CONCLUSIONS:
APM degeneration and replacement with fat in Androgenetic Alopecia has not previously been described. The underlying mechanism remains to be determined. However, we speculate that this phenomenon might be related to depletion of stem or progenitor cells from the follicle mesenchyme, explaining why Androgenetic Alopecia is treatment resistant.

© 2014 British Association of Dermatologists.


Miniaturized Hairs Maintain Contact with the Arrector Pili Muscle in Alopecia Areata but not in Androgenetic Alopecia: A Model for Reversible Miniaturization and Potential for Hair Regrowth
Anousha Yazdabadi,1,2 D Whiting,3 Norwood Rufaut,1,2 and R Sinclair1,2
Author information ► Copyright and License information ► Disclaimer

This article has been cited by other articles in PMC.

Go to:
Abstract
Go to:
Background:
Hair follicle miniaturization is the hallmark of male pattern hair loss (MPHL), female pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for complete hair regrowth and reversal of miniaturization. MPHL and FPHL are either irreversible or show only partial regrowth and minimal reversal of miniaturization. Hypothesis: The arrector pili muscle (APM) attachment to the hair follicle bulge, a recognized repository of stem cells may be necessary for reversal of hair follicle miniaturization.

Go to:
Materials and Methods:
Sequential histological sections from MPHL, FPHL, AA, and telogen effluvium were used to create three-dimensional images to compare the relationship between the APM and bulge.

Go to:
Results:
In AA, contact was maintained between the APM and the bulge of miniaturized follicles while in MPHL and FPHL contact was lost.

Go to:
Discussion:
Contact between the APM and the bulge in AA may be required for reversal of hair follicle miniaturization. Maintenance of contact between miniaturized follicles in AA could explain the complete hair regrowth while loss of contact between the APM and the bulge in MPHL and FPHL may explain why the hair loss is largely irreversible. This loss of contact may reflect changes in stem cell biology that also underlie irreversible miniaturization.

Keywords:










= GATA3-induced hyper-activated sebum production in abnormal components of the hair follicle destroys the Arrector pili muscle and detaches/destroys the hair bulb, which is rich in https://en.wikipedia.org/wiki/Chondroitin_sulfate -rich protoglycans- from the https://en.wikipedia.org/wiki/Outer_root_sheath of the hair follicle- and is caused(at least in part- if not mostly) by reduced hedgehog signalling via reduced SOX9 expression(which regulates https://en.wikipedia.org/wiki/Chondrogenesis to produce the protoglycans that make up the hair bulb, as seen in the photo above)- and of which is a critical regulator of stem cell-secreted growth factors- all the way up the cascade:



SOX9: a stem cell transcriptional regulator of secreted niche signaling factors

1. Meelis Kadaja1,
2. Brice E. Keyes1,
3. Mingyan Lin2,
4. H. Amalia Pasolli1,
5. Maria Genander1,
6. Lisa Polak1,
7. Nicole Stokes1,
8. Deyou Zheng2,3,4 and
9. Elaine Fuchs1,5

+Author Affiliations

1. 1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA;
2. 2Department of Genetics,
3. 3Department of Neurology,
4. 4Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA

Abstract
Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.










As mentioned in the 1st study aof this thread, it's stated Hedgehog signalling(aka cell proliferation) is the most downregulated pathway in Androgenetic Alopecia tissue, while T cell receptor signalling is the most upregulated(aka inflammation)

So:

https://en.wikipedia.org/wiki/SOX9 down(downstream target of Hedgehog signalling) = https://en.wikipedia.org/wiki/GATA3 up(downstream target of T cell receptor signalling)

= Androgenetic Alopecia

 

[EndlessPossibilities]

the answer to your question is simple:

Just the Hedgehog signalling pathway, for being the most downregulated pathway in alopecic tissues.



Hedgehog signaling stimulates the conversion of cholesterol to steroids

Abstract
Cholesterol modification of Hedgehog (Hh) ligands is fundamental for the activity of Hh signaling, and cholesterol biosynthesis is also required for intracellular Hh signaling transduction. Here, we investigated the roles and underlying mechanism of Hh signaling in metabolism of cholesterol. The main components of the Hh pathway are abundantly expressed in both human cytotrophoblasts and trophoblast-like cells. Activation of Hh signaling induces the conversion of cholesterol to progesterone (P4) and estradiol (E2) through up-regulating the expression of steroidogenic enzymes including P450 cholesterol side chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1), and aromatase. Moreover, inhibition of Hh signaling attenuates not only Hh-induced expression of steroidogenic enzymes but also the conversion of cholesterol to P4 and E2. Whereas Gli3 is required for Hh-induced P450scc expression, Gli2 mediates the induction of 3β-HSD1 and aromatase. Finally, in ovariectomized nude mice, systemic inhibition of Hh signaling by cyclopamine suppresses circulating P4 and E2 levels derived from a trophoblast-like choricarcinoma xenograft, and attenuates uterine response to P4 and E2. Together these results uncover a hitherto uncharacterized role of Hh signaling in metabolism of cholesterol.


Gli2 is the effector gene of the Hedgehog pathway- meaning it's the most terminal, major downstream gene that finalises the execution of Hedgehog signalling.


The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity

ABSTRACT
Different tissues contain diverse and dynamic cellular niches, providing distinct signals to tissue-resident or migratory infiltrating immune cells. Hedgehog (Hh) proteins are secreted inter-cellular signalling molecules, which are essential during development and are important in cancer, post-natal tissue homeostasis and repair. Hh signalling mediated by the Hh-responsive transcription factor Gli2 also has multiple roles in T-lymphocyte development and differentiation. Here, we investigate the function of Gli2 in T-cell signalling and activation. Gene transcription driven by the Gli2 transcriptional activator isoform (Gli2A) attenuated T-cell activation and proliferation following T-cell receptor (TCR) stimulation. Expression of Gli2A in T-cells altered gene expression profiles, impaired the TCR-induced Ca2+ flux and nuclear expression of NFAT2, suppressed upregulation of molecules essential for activation, and attenuated signalling pathways upstream of the AP-1 and NFκB complexes, leading to reduced activation of these important transcription factors. Inhibition of physiological Hh-dependent transcription increased NFκB activity upon TCR ligation. These data are important for understanding the molecular mechanisms of immunomodulation, particularly in tissues where Hh proteins or other Gli-activating ligands such as TGFβ are upregulated, including during inflammation, tissue damage and repair, and in tumour microenvironments.






This means once hedgehog signalling is activated via Gli2, T cell activation is impaired(inflammation inhibition- allowing cell to profilerate instead of being attacked by T cells).

In other words, u automatically stop inflammation once Hedgehog signalling is activated.

Progesterone and Estradiol would be the solution- they are the end-products of activated Hegdehog signalling, as per above.

Throw in Calcitriol too if you're Caucasian(as per above also)

Progesterone in alopecic tissues will resolve Insulin/IGF-1(PGD2 comes from Insulin/IGF-1 activating mast cells in sebocytes),5 Alpha redutase and inflammation. Progesterone shifts cytokine profile to https://en.wikipedia.org/wiki/Regulatory_T_cell , is a tumor suppressor and is to keep hedgehog signalling in check. This is the reason why Progesterone up to 2% can be bought OTC in nutritional form, but not Estradiol. They reduce the size of prostates and prevent Breast tenderness.

A simple way of understanding the function of Treg cells is pregnancy. Think of the growing hair follicle as a 'fetus'.

The growting fetus in a mother's body is a 'foreign' object by nature. Treg cells prevents the mother's T cells from attacking the fetus

Progesterone increases systemic and local uterine proportions of CD4+CD25+ Treg cells during midterm pregnancy in mice.

Abstract
Mechanisms maintaining the growth of a "semi-foreign" fetus within the maternal uterus via immune tolerance remain unclear. CD4(+)CD25(+) regulatory T (Treg) cells have been implicated in the maintenance of maternal-fetal immune tolerance. Additionally, 17β-estradiol (E2) is able to initiate immune suppression through CD4(+)CD25(+) Treg cells during early pregnancy. Little is known, however, regarding the relationship between progesterone (P4) and immune tolerance during midterm pregnancy, an important period, characterized by higher levels of P4 but lower levels of E2 in the serum. Here, we examined the effects of P4 on the expansion and function of systemic and local uterine CD4(+)CD25(+) Treg cells during midterm pregnancy in mice. Using in vivo and in vitro models, we provide the first evidence that P4 not only increases the proportion of CD4(+)CD25(+) Treg cells and IL-10 expression but also enhances their suppressive function. Moreover, at physiological doses relevant to midterm pregnancy, P4, but not E2, converts CD4(+)CD25(-) T cells into CD4(+)CD25(+) Treg cells. This conversion was inhibited in vitro by the nuclear P4 receptors antagonist RU 486 and in vivo in P4-treated ovariectomized and pseudopregnant mice models, suggesting that P4 expands Treg populations via nuclear P4 receptors. Furthermore, RU 486 significantly reduced the quantity and function of Treg cells in the fetal-maternal interface before the onset of induced abortion. Interestingly, with decreasing Foxp3, proinflammatory factors increased. Together, the present results demonstrate that P4 is an important regulator of systemic and local CD4(+)CD25(+) Treg cells, which are involved in maintaining maternal-fetal immune tolerance during midterm pregnancy.




Estradiol itself in alopecic tissue provides PGE2(from PGE2's receptors EP2/EP4- comes WNT signalling), SHBG, is inflammatory in nature that it shifts ceullar cytokine balance towards Th17 away from Th2(which is dominant in PGD2). Hence if u use only Estradiol, u will still get inflammation. Estradiol is an oncogene itself- it cannot be bought OTC and goes by prescription only. Progesterone is to counter the oncogenic effects of Estradiol, Estrone and Androgens- allowing controlled cellular growth.

This is the reason why normal hair-bearing tissues secretes Progesterone(inhibitor of T cell Receptor signalling aka inflammation) and Estradiol(activator of cellular proliferation) together- they are the end-products of Hegdehog signalling and in the context of hair growth- the dual initiators and providers of maintanence.

In simple terms, Progesterone allows the hair follicle to grow without being attacked by providing a 'protective shield'(aka https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD200 ) around the hair follicle, while Estradiol allows the growth of the hair follicle itself by inducing numerous growth factors.

If you inhibit production of Progesterone and Estradiol, Testosterone(and hence- DHT) is greatly boosted- because these 3 types of sex steroids are the major hormones in the Steroidogenic pathway.

Bro you read this all wrong. First off. Igf1 grows hair.

so what has the PGD2 and adipogenesis(fat growth) got to do with arretor pili muscle?




Destruction of the arrector pili muscle and fat infiltration in androgenic alopecia.
Torkamani N1, Rufaut Norwood, Jones L, Sinclair R.
Author information

Abstract
BACKGROUND:
Androgenic alopecia (Androgenetic Alopecia) is the most common hair loss condition in men and women. Hair loss is caused by follicle miniaturization, which is largely irreversible beyond a certain degree of follicular regression. In contrast, hair loss in telogen effluvium (Telogen Effluvium) is readily reversible. The arrector pili muscle (APM) connects the follicle to the surrounding skin.

OBJECTIVES:
To compare histopathological features of the APM in Androgenetic Alopecia and Telogen Effluvium.

METHODS:
Archival blocks of 4-mm scalp punch biopsies from eight patients with Androgenetic Alopecia and five with Telogen Effluvium were obtained. New 4-mm biopsies from five normal cases were used as controls. Serial 7-μm sections were stained with a modified Masson's trichrome stain. 'Reconstruct' software was used to construct and evaluate three-dimensional images of the follicle and APM.

RESULTS:
The APM degenerated and was replaced by adipose tissue in all Androgenetic Alopecia specimens. Remnants of the APM remained attached to the hair follicle. There was no fat in the normal skin specimens. Fat was seen in two of five Telogen Effluvium specimens but could be attributed to these patients also showing evidence of Androgenetic Alopecia. Quantitative analysis showed that muscle volume decreased and fat volume increased significantly (P < 0·05) in Androgenetic Alopecia compared with controls.

CONCLUSIONS:
APM degeneration and replacement with fat in Androgenetic Alopecia has not previously been described. The underlying mechanism remains to be determined. However, we speculate that this phenomenon might be related to depletion of stem or progenitor cells from the follicle mesenchyme, explaining why Androgenetic Alopecia is treatment resistant.

© 2014 British Association of Dermatologists.


Miniaturized Hairs Maintain Contact with the Arrector Pili Muscle in Alopecia Areata but not in Androgenetic Alopecia: A Model for Reversible Miniaturization and Potential for Hair Regrowth
Anousha Yazdabadi,1,2 D Whiting,3 Norwood Rufaut,1,2 and R Sinclair1,2
Author information ► Copyright and License information ► Disclaimer

This article has been cited by other articles in PMC.

Go to:
Abstract
Go to:
Background:
Hair follicle miniaturization is the hallmark of male pattern hair loss (MPHL), female pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for complete hair regrowth and reversal of miniaturization. MPHL and FPHL are either irreversible or show only partial regrowth and minimal reversal of miniaturization. Hypothesis: The arrector pili muscle (APM) attachment to the hair follicle bulge, a recognized repository of stem cells may be necessary for reversal of hair follicle miniaturization.

Go to:
Materials and Methods:
Sequential histological sections from MPHL, FPHL, AA, and telogen effluvium were used to create three-dimensional images to compare the relationship between the APM and bulge.

Go to:
Results:
In AA, contact was maintained between the APM and the bulge of miniaturized follicles while in MPHL and FPHL contact was lost.

Go to:
Discussion:
Contact between the APM and the bulge in AA may be required for reversal of hair follicle miniaturization. Maintenance of contact between miniaturized follicles in AA could explain the complete hair regrowth while loss of contact between the APM and the bulge in MPHL and FPHL may explain why the hair loss is largely irreversible. This loss of contact may reflect changes in stem cell biology that also underlie irreversible miniaturization.

Keywords:










= GATA3-induced hyper-activated sebum production in abnormal components of the hair follicle destroys the Arrector pili muscle and detaches/destroys the hair bulb, which is rich in https://en.wikipedia.org/wiki/Chondroitin_sulfate -rich protoglycans- from the https://en.wikipedia.org/wiki/Outer_root_sheath of the hair follicle- and is caused(at least in part- if not mostly) by reduced hedgehog signalling via reduced SOX9 expression(which regulates https://en.wikipedia.org/wiki/Chondrogenesis to produce the protoglycans that make up the hair bulb, as seen in the photo above)- and of which is a critical regulator of stem cell-secreted growth factors- all the way up the cascade:



SOX9: a stem cell transcriptional regulator of secreted niche signaling factors

1. Meelis Kadaja1,
2. Brice E. Keyes1,
3. Mingyan Lin2,
4. H. Amalia Pasolli1,
5. Maria Genander1,
6. Lisa Polak1,
7. Nicole Stokes1,
8. Deyou Zheng2,3,4 and
9. Elaine Fuchs1,5

+Author Affiliations

1. 1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA;
2. 2Department of Genetics,
3. 3Department of Neurology,
4. 4Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA

Abstract
Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.










As mentioned in the 1st study aof this thread, it's stated Hedgehog signalling(aka cell proliferation) is the most downregulated pathway in Androgenetic Alopecia tissue, while T cell receptor signalling is the most upregulated(aka inflammation)

So:

https://en.wikipedia.org/wiki/SOX9 down(downstream target of Hedgehog signalling) = https://en.wikipedia.org/wiki/GATA3 up(downstream target of T cell receptor signalling)

= Androgenetic Alopecia

Problem with a lot of the genetic studies is they examine balding scalp tissue genes when we should be looking for the genes that make men immune to balding.

these studies are basically most likely documenting epigenetic changes that have happened in other words much of these genes are not encoded in the base dna. You would probably not find these changes in gene expression when they are young.



Also while I beleive you interpreted many of the studies incorrectly. You came on the right conclusion somehow. That is. The issue is inflammation. Yes we know. What we all are dying to know is the cause of that inflammation. That’s the cure