https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.14278 <=== ( use sci-hub for full study )
Genomewide differential expression profiling of long non‐coding RNAs in androgenetic alopecia in a Chinese male population
Abstract
Background
Androgenetic alopecia (Androgenetic Alopecia), or male pattern baldness (male pattern baldness), is the most common form of hair loss in males. A combination of genetic and androgen causes have been suggested as factors that contribute to the development of Androgenetic Alopecia. However, the specific molecular mechanisms that underly Androgenetic Alopecia remain largely unknown. Long non‐coding RNAs (lncRNAs), a new class of regulatory non‐coding RNAs that are longer than 200 nucleotides, have been shown to play important roles in a number of cellular processes, including transcription, chromosome remodelling and post‐transcriptional processing. The dysregulation of lncRNAs is associated with many forms of diseases, but it remains unknown whether lncRNAs are associated with Androgenetic Alopecia.
Objective
The aim of this study was to identify Androgenetic Alopecia‐associated lncRNAs and predict the potential roles of these lncRNAs in Androgenetic Alopecia.
Methods
A genomewide microarray was used to identify lncRNAs that are differentially expressed between Androgenetic Alopecia and adjacent normal tissues. Real‐time qRT‐PCR was used to validate the microarray data.
Results
A large number of lncRNAs were differentially expressed (fold change >2.4) between Androgenetic Alopecia and adjacent normal tissues. Of these, 770 were upregulated and 1373 were downregulated. Moreover, pathway analysis revealed that 53 functional pathways were associated with the upregulated transcripts, while 11 pathways were associated with the downregulated transcripts.
Conclusion
To our knowledge, this is the first study to investigate Androgenetic Alopecia‐associated lncRNAs. lncRNA profiles are altered in Androgenetic Alopecia, and these lncRNAs and their target genes may serve as novel candidates for preventing and treating Androgenetic Alopecia.
"Of these, T-cell receptor signalling was the most upregulated pathway, and Hedgehog signalling pathway was the most downregulated pathway. The Hedgehog pathway has been a focus of research in recent years. The Hedgehog pathway has been shown to be closely related to hair cycle control, and the inhibition of this pathway can lead to hair loss, in alignment with our results.17,18 The T-cell receptor signalling pathway plays important roles in human immune functions.19 It has been reported that this pathway is associated with the generation of alopecia areata, which is an autoimmune disease.19 However, a relationship between Androgenetic Alopecia and this pathway had not previously been reported. Our results reveal that Androgenetic Alopecia might be significantly and importantly involved with the immune system, but this requires further investigation. Among the most differentially expressed lncRNAs, some are closely related to coding genes, such as CTD-2636A23.2, which is associated with the coding gene HMGCS1. This gene was shown to be associated with cellular responses to follicle stimulating hormone stimuli, cellular responses to cholesterol, cholesterol biosynthetic processes and male gonad development( aka testicles), all of which are tightly associated with Androgenetic Alopecia mechanisms.20–23 The lncRNAs RP4-742J24.2 and AC137932.5 are related to the coding genes BTBD3 and ANKRD11, respectively. ANKRD11 has been found to be associated with tissue homoeostasis,24 and BTBD3 is related to cerebral cortex development.25 Other lncRNAs, such as RP11-818024.3 and RP11-76908.2, are associated with the genes CRK and YES1, respectively, which are involved in ion channel binding, the vascular endothelial growth factor receptor signalling pathway, cellular responses to transforming growth factor-beta and platelet-derived factor.26–29 It is interesting to note that the functions of these genes are associated with the processes underlying and the development of Androgenetic Alopecia."
So 1 of these significantly, differentially expressed incRNAs is(2nd most downregulated gene in alopecic scalp- 33+ folds lower than adjacent normal scalp tissue);
ASHGV40041683 33.8073415 Down ENST0000 0565748 CTD2636A23.2 GENCODE 5 Natural antisense HMGCS1 Hydroxy methylglutarylCoA synthase
https://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_synthase
it's main function is in the cholesterol biosynthetic and cellular reponses to cholesterol pathway. In other words, it's associated with cholesterol. we are going to need to increase HMGCS1 in Androgenetic Alopecia scalp.
HMGCS1 is activated by https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factor_4_alpha
Interactions[edit]
Hepatocyte nuclear factor 4 alpha has been shown to interact with:
https://www.ncbi.nlm.nih.gov/pubmed/19088433
Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP.
Vock C1, Döring F, Nitz I.
Author information
Abstract
The acyl-CoA binding protein (ACBP) is an ubiquitary expressed multi-functional protein which regulates basic cellular functions such as fatty acid and steroid metabolism. Since ACBP is described to interact with the transcription factor hepatocyte nuclear factor 4 alpha (HNF-4alpha), we investigated the role of human ACBP on transcriptional regulation of the putative HNF-4alpha target gene HMG-CoA synthase 1 (HMGCS1). As shown by promoter-reporter assays ACBP represses the HNF-4alpha-induced activity of a 617bp HMGCS1 promoter fragment by approximately 80% in HepG2 cells as well as in non-endodermal HeLa cells devoid of HNF-4alpha. Interestingly, reporter assays without co-transfection of HNF-4alpha revealed that ACBP reduces the activity of the HMGCS1 promoter by about 60 to 80% in both cell lines. Activities of 417bp and 317bp HMGCS1 promoter fragments were 2.5 to 4 fold decreased by ACBP. Concordantly, the levels of HMGCS1-mRNA and -protein were diminished to 60% and 70% in ACBP-expressing HeLa cells, respectively. Additionally, ACBP reduces the promoter activity and the mRNA levels of the cholesterogenic HMG-CoA reductase (HMGCR). In conclusion, we provide evidence that ACBP is a transcriptional regulator of the HMGCS1 and HMGCR genes encoding rate-limiting enzymes of cholesterol synthesis pathway.
and low levels of HNF4A = loss of lipid homeostasis
https://www.ncbi.nlm.nih.gov/pubmed/21071704
CONCLUSIONS:
Loss of hepatic HNF4α results in severe lipid disorder as a result of dysregulation of multiple genes involved in lipid metabolism. In contrast, augmentation of hepatic HNF4α activity lowers plasma cholesterol levels but has no effect on plasma triglyceride levels because of selective gene regulation. Our data indicate that hepatic HNF4α is essential for controlling the basal expression of numerous genes involved in lipid metabolism and is indispensable for maintaining normal lipid homeostasis.[/quote]
Not to mention HNF4A is tied up with SHBG levels https://en.wikipedia.org/wiki/Sex_hormone-binding_globulin . SHBG renders circulating hormones to the inactive state- estrogens and androgens.
Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%) and corticosteroid-binding globulin (CBG) (AKA transcortin), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1-2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG.
Promoter activation[edit]
The mechanism of activating the promoter for SHBG in the liver involves hepatocyte nuclear factor 4 alpha (HNF4A) binding to a DR1 like cis element which then stimulate production. Competing with HNF4A at a third site on the promoter is PPARG-2 which reduces copying the gene to RNA. If HNF4A level is low then COUP-TF binds to the first site and turns off production of SHBG.[5]
So low levels of HNF4A = low levels of SHBG.
So to increase HNF4A, https://examine.com/supplements/berberine/ is an option as seen in Wiki:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760199/
"Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner"
Now the most upregulated gene in alopecic scalp,from the study- is:
http://www.genecards.org/cgi-bin/carddisp.pl?gene=PRAC2 (69+folds higher than adjacent normal scalp tissue)
ASHGV40021887 69.7530454 Up NM_001282275 PRAC2 17 Hs.236557 Prostate cancer susceptibility candidate 2
Prostate Cancer Susceptibility Candidate 2
This gene is highly expressed in prostate, rectum, colon, and testis. This gene may produce a non-coding RNA or may encode a short protein that might localize to the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
https://www.ncbi.nlm.nih.gov/pubmed/12746837
PRAC2: a new gene expressed in human prostate and prostate cancer.
Olsson P1, Motegi A, Bera TK, Lee B, Pastan I.
Author information
Abstract
BACKGROUND:
The database of human Expressed Sequence Tags was previously used to identify PRAC (Prostate 47:125-131, 2001), a novel gene specifically expressed in human prostate, prostate cancer, rectum, and distal colon. In this report, we have identified PRAC2, another gene with a similar expression pattern that is located adjacent to the original PRAC gene on chromosome 17q21.3.
METHODS:
Using a computer-based analysis, a cluster of sequence homologous ESTs was identified that is mainly derived from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT-PCR. The PRAC2 transcript and protein were identified using Northern blot analysis, RACE-PCR, primer extension, and Western blots.
RESULTS:
PRAC2 encodes a 564 nucleotide RNA found in prostate, rectum, distal colon, and testis. Weak expression was also found in placenta, peripheral blood leukocytes, skin, and in two prostate cancer cell lines: LNCaP and PC-3. The transcript seems to encode a 10.5-kDa nuclear protein. The PRAC2 gene is located on chromosome 17 at position 17q21, between the Hoxb-13 gene and the recently discovered PRAC gene.
CONCLUSIONS:
Because of the higher expression of PRAC2 in prostate and its proximity to Hoxb-13, PRAC2 may have a function in prostate growth and development.
Cholesterol and Prostate cancer(in addition to the former being a precursor to sex hormones and vitamin D)- is correlated:
https://www.sciencedirect.com/science/article/pii/S0304419X13000036
Cholesterol accumulation in prostate cancer: A classic observation from a modern perspective
Abstract
Prostate cancer (PCa) is the most common cancer in men in developed countries. Epidemiological studies have associated high blood-cholesterol levels with an increased risk of PCa, whilst cholesterol-lowering drugs (statins) reduce the risk of advanced PCa. Furthermore, normal prostate epithelial cells have an abnormally high cholesterol content, with cholesterol levels increasing further during progression to PCa. In this review, we explore why and how this occurs.
Concurrent to this observation, intense efforts have been expended in cardiovascular research to better understand the regulators of cholesterol homeostasis. Here, we apply this knowledge to elucidate the molecular mechanisms driving the accumulation of cholesterol in PCa. For instance, recent evidence from our group and others shows that major signalling players in prostate growth and differentiation, such as androgens and Akt, modulate the key transcriptional regulators of cholesterol homeostasis to enhance cholesterol levels. This includes adjusting central carbon metabolism to sustain greater lipid synthesis. Perturbations in cholesterol homeostasis appear to be maintained even when PCa approaches the advanced, ‘castration-resistant’ state. Overall, this provides a link between cholesterol accumulation and PCa cell growth. Given there is currently no cure for castration-resistant PCa, could cholesterol metabolism be a novel target for PCa therapy?
Overall, this review presents a picture that cholesterol metabolism is important for PCa development: growth-promoting factors stimulate cholesterol accumulation, which in turn presents a possible target for chemotherapy. Consequently, we recommend future investigations, both to better elucidate the mechanisms driving this accumulation and applying it in novel chemotherapeutic strategies.
and we know Androgenetic Alopecia is largely caused by an abhorrent level of lipid synthesis in the scalp:
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.14767 (<== use sci hub for full study)
We identified 1,339 differential transcripts between samples from Cluster III and II (Figure 2B and G), and found up-regulation of metabolism (electron carrier activity, respiratory chain and monosaccharide metabolic process), lipid biosynthesis, response to hormone stimulus and steroid hormone biosynthesis related genes (Figure 2F, Table S2, S5). The up-regulation of genes in the respiratory chain (CYB5R3, SDHA) may impact on the redox state in Androgenetic Alopecia-affected hairs 7, 8. Furthermore, the up-regulation of anti-oxidation genes (GPX4 and PRX3) suggests that patient vertex scalps may be exposed to greater oxidative stress than control scalps, possibly resultant from increased respiratory chain activity 9, 10. Increased levels of GPX4 would also protect the increased amount of lipid synthesized in the patient vertex scalp from phospholipid hydroperoxides-mediated oxidation
What we can gather here is the major mechanism of Androgenetic Alopecia is an involvement of Cholesterol and the resulting downstream mechanisms(sex hormones and even downstream lipids like prostaglandins and leukotrienes)
Genomewide differential expression profiling of long non‐coding RNAs in androgenetic alopecia in a Chinese male population
Abstract
Background
Androgenetic alopecia (Androgenetic Alopecia), or male pattern baldness (male pattern baldness), is the most common form of hair loss in males. A combination of genetic and androgen causes have been suggested as factors that contribute to the development of Androgenetic Alopecia. However, the specific molecular mechanisms that underly Androgenetic Alopecia remain largely unknown. Long non‐coding RNAs (lncRNAs), a new class of regulatory non‐coding RNAs that are longer than 200 nucleotides, have been shown to play important roles in a number of cellular processes, including transcription, chromosome remodelling and post‐transcriptional processing. The dysregulation of lncRNAs is associated with many forms of diseases, but it remains unknown whether lncRNAs are associated with Androgenetic Alopecia.
Objective
The aim of this study was to identify Androgenetic Alopecia‐associated lncRNAs and predict the potential roles of these lncRNAs in Androgenetic Alopecia.
Methods
A genomewide microarray was used to identify lncRNAs that are differentially expressed between Androgenetic Alopecia and adjacent normal tissues. Real‐time qRT‐PCR was used to validate the microarray data.
Results
A large number of lncRNAs were differentially expressed (fold change >2.4) between Androgenetic Alopecia and adjacent normal tissues. Of these, 770 were upregulated and 1373 were downregulated. Moreover, pathway analysis revealed that 53 functional pathways were associated with the upregulated transcripts, while 11 pathways were associated with the downregulated transcripts.
Conclusion
To our knowledge, this is the first study to investigate Androgenetic Alopecia‐associated lncRNAs. lncRNA profiles are altered in Androgenetic Alopecia, and these lncRNAs and their target genes may serve as novel candidates for preventing and treating Androgenetic Alopecia.
From the analysis, of the downregulated genes, the Hedgehog signalling pathway was the most enriched network and it consisted of five target genes that were signifi- cantly differentially expressed between the two samples, while the most enriched upregulated genes were associated with the Tcell receptor signalling pathway, which consisted of 26 target genes that were found to be significantly differentially expressed between Androgenetic Alopecia and adjacent normal tissues. Figure 7a shows the top 10 upregulated pathways, and Figure 7b shows the top 10 downregulated pathways.
"Of these, T-cell receptor signalling was the most upregulated pathway, and Hedgehog signalling pathway was the most downregulated pathway. The Hedgehog pathway has been a focus of research in recent years. The Hedgehog pathway has been shown to be closely related to hair cycle control, and the inhibition of this pathway can lead to hair loss, in alignment with our results.17,18 The T-cell receptor signalling pathway plays important roles in human immune functions.19 It has been reported that this pathway is associated with the generation of alopecia areata, which is an autoimmune disease.19 However, a relationship between Androgenetic Alopecia and this pathway had not previously been reported. Our results reveal that Androgenetic Alopecia might be significantly and importantly involved with the immune system, but this requires further investigation. Among the most differentially expressed lncRNAs, some are closely related to coding genes, such as CTD-2636A23.2, which is associated with the coding gene HMGCS1. This gene was shown to be associated with cellular responses to follicle stimulating hormone stimuli, cellular responses to cholesterol, cholesterol biosynthetic processes and male gonad development( aka testicles), all of which are tightly associated with Androgenetic Alopecia mechanisms.20–23 The lncRNAs RP4-742J24.2 and AC137932.5 are related to the coding genes BTBD3 and ANKRD11, respectively. ANKRD11 has been found to be associated with tissue homoeostasis,24 and BTBD3 is related to cerebral cortex development.25 Other lncRNAs, such as RP11-818024.3 and RP11-76908.2, are associated with the genes CRK and YES1, respectively, which are involved in ion channel binding, the vascular endothelial growth factor receptor signalling pathway, cellular responses to transforming growth factor-beta and platelet-derived factor.26–29 It is interesting to note that the functions of these genes are associated with the processes underlying and the development of Androgenetic Alopecia."
So 1 of these significantly, differentially expressed incRNAs is(2nd most downregulated gene in alopecic scalp- 33+ folds lower than adjacent normal scalp tissue);
ASHGV40041683 33.8073415 Down ENST0000 0565748 CTD2636A23.2 GENCODE 5 Natural antisense HMGCS1 Hydroxy methylglutarylCoA synthase
https://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_synthase
it's main function is in the cholesterol biosynthetic and cellular reponses to cholesterol pathway. In other words, it's associated with cholesterol. we are going to need to increase HMGCS1 in Androgenetic Alopecia scalp.
HMGCS1 is activated by https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factor_4_alpha
Interactions[edit]
Hepatocyte nuclear factor 4 alpha has been shown to interact with:
- Beta-catenin,[15]
- CREB binding protein,[16][17]
- MED1,[18][19]
- MED14,[18][19]
- Small heterodimer partner[20]
- Testicular receptor 4,[21]
https://www.ncbi.nlm.nih.gov/pubmed/19088433
Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP.
Vock C1, Döring F, Nitz I.
Author information
Abstract
The acyl-CoA binding protein (ACBP) is an ubiquitary expressed multi-functional protein which regulates basic cellular functions such as fatty acid and steroid metabolism. Since ACBP is described to interact with the transcription factor hepatocyte nuclear factor 4 alpha (HNF-4alpha), we investigated the role of human ACBP on transcriptional regulation of the putative HNF-4alpha target gene HMG-CoA synthase 1 (HMGCS1). As shown by promoter-reporter assays ACBP represses the HNF-4alpha-induced activity of a 617bp HMGCS1 promoter fragment by approximately 80% in HepG2 cells as well as in non-endodermal HeLa cells devoid of HNF-4alpha. Interestingly, reporter assays without co-transfection of HNF-4alpha revealed that ACBP reduces the activity of the HMGCS1 promoter by about 60 to 80% in both cell lines. Activities of 417bp and 317bp HMGCS1 promoter fragments were 2.5 to 4 fold decreased by ACBP. Concordantly, the levels of HMGCS1-mRNA and -protein were diminished to 60% and 70% in ACBP-expressing HeLa cells, respectively. Additionally, ACBP reduces the promoter activity and the mRNA levels of the cholesterogenic HMG-CoA reductase (HMGCR). In conclusion, we provide evidence that ACBP is a transcriptional regulator of the HMGCS1 and HMGCR genes encoding rate-limiting enzymes of cholesterol synthesis pathway.
and low levels of HNF4A = loss of lipid homeostasis
https://www.ncbi.nlm.nih.gov/pubmed/21071704
CONCLUSIONS:
Loss of hepatic HNF4α results in severe lipid disorder as a result of dysregulation of multiple genes involved in lipid metabolism. In contrast, augmentation of hepatic HNF4α activity lowers plasma cholesterol levels but has no effect on plasma triglyceride levels because of selective gene regulation. Our data indicate that hepatic HNF4α is essential for controlling the basal expression of numerous genes involved in lipid metabolism and is indispensable for maintaining normal lipid homeostasis.[/quote]
Not to mention HNF4A is tied up with SHBG levels https://en.wikipedia.org/wiki/Sex_hormone-binding_globulin . SHBG renders circulating hormones to the inactive state- estrogens and androgens.
Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%) and corticosteroid-binding globulin (CBG) (AKA transcortin), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1-2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG.
Promoter activation[edit]
The mechanism of activating the promoter for SHBG in the liver involves hepatocyte nuclear factor 4 alpha (HNF4A) binding to a DR1 like cis element which then stimulate production. Competing with HNF4A at a third site on the promoter is PPARG-2 which reduces copying the gene to RNA. If HNF4A level is low then COUP-TF binds to the first site and turns off production of SHBG.[5]
So low levels of HNF4A = low levels of SHBG.
So to increase HNF4A, https://examine.com/supplements/berberine/ is an option as seen in Wiki:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760199/
"Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner"
Now the most upregulated gene in alopecic scalp,from the study- is:
http://www.genecards.org/cgi-bin/carddisp.pl?gene=PRAC2 (69+folds higher than adjacent normal scalp tissue)
ASHGV40021887 69.7530454 Up NM_001282275 PRAC2 17 Hs.236557 Prostate cancer susceptibility candidate 2
Prostate Cancer Susceptibility Candidate 2
This gene is highly expressed in prostate, rectum, colon, and testis. This gene may produce a non-coding RNA or may encode a short protein that might localize to the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
https://www.ncbi.nlm.nih.gov/pubmed/12746837
PRAC2: a new gene expressed in human prostate and prostate cancer.
Olsson P1, Motegi A, Bera TK, Lee B, Pastan I.
Author information
Abstract
BACKGROUND:
The database of human Expressed Sequence Tags was previously used to identify PRAC (Prostate 47:125-131, 2001), a novel gene specifically expressed in human prostate, prostate cancer, rectum, and distal colon. In this report, we have identified PRAC2, another gene with a similar expression pattern that is located adjacent to the original PRAC gene on chromosome 17q21.3.
METHODS:
Using a computer-based analysis, a cluster of sequence homologous ESTs was identified that is mainly derived from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT-PCR. The PRAC2 transcript and protein were identified using Northern blot analysis, RACE-PCR, primer extension, and Western blots.
RESULTS:
PRAC2 encodes a 564 nucleotide RNA found in prostate, rectum, distal colon, and testis. Weak expression was also found in placenta, peripheral blood leukocytes, skin, and in two prostate cancer cell lines: LNCaP and PC-3. The transcript seems to encode a 10.5-kDa nuclear protein. The PRAC2 gene is located on chromosome 17 at position 17q21, between the Hoxb-13 gene and the recently discovered PRAC gene.
CONCLUSIONS:
Because of the higher expression of PRAC2 in prostate and its proximity to Hoxb-13, PRAC2 may have a function in prostate growth and development.
Cholesterol and Prostate cancer(in addition to the former being a precursor to sex hormones and vitamin D)- is correlated:
https://www.sciencedirect.com/science/article/pii/S0304419X13000036
Cholesterol accumulation in prostate cancer: A classic observation from a modern perspective
Abstract
Prostate cancer (PCa) is the most common cancer in men in developed countries. Epidemiological studies have associated high blood-cholesterol levels with an increased risk of PCa, whilst cholesterol-lowering drugs (statins) reduce the risk of advanced PCa. Furthermore, normal prostate epithelial cells have an abnormally high cholesterol content, with cholesterol levels increasing further during progression to PCa. In this review, we explore why and how this occurs.
Concurrent to this observation, intense efforts have been expended in cardiovascular research to better understand the regulators of cholesterol homeostasis. Here, we apply this knowledge to elucidate the molecular mechanisms driving the accumulation of cholesterol in PCa. For instance, recent evidence from our group and others shows that major signalling players in prostate growth and differentiation, such as androgens and Akt, modulate the key transcriptional regulators of cholesterol homeostasis to enhance cholesterol levels. This includes adjusting central carbon metabolism to sustain greater lipid synthesis. Perturbations in cholesterol homeostasis appear to be maintained even when PCa approaches the advanced, ‘castration-resistant’ state. Overall, this provides a link between cholesterol accumulation and PCa cell growth. Given there is currently no cure for castration-resistant PCa, could cholesterol metabolism be a novel target for PCa therapy?
Overall, this review presents a picture that cholesterol metabolism is important for PCa development: growth-promoting factors stimulate cholesterol accumulation, which in turn presents a possible target for chemotherapy. Consequently, we recommend future investigations, both to better elucidate the mechanisms driving this accumulation and applying it in novel chemotherapeutic strategies.
and we know Androgenetic Alopecia is largely caused by an abhorrent level of lipid synthesis in the scalp:
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.14767 (<== use sci hub for full study)
We identified 1,339 differential transcripts between samples from Cluster III and II (Figure 2B and G), and found up-regulation of metabolism (electron carrier activity, respiratory chain and monosaccharide metabolic process), lipid biosynthesis, response to hormone stimulus and steroid hormone biosynthesis related genes (Figure 2F, Table S2, S5). The up-regulation of genes in the respiratory chain (CYB5R3, SDHA) may impact on the redox state in Androgenetic Alopecia-affected hairs 7, 8. Furthermore, the up-regulation of anti-oxidation genes (GPX4 and PRX3) suggests that patient vertex scalps may be exposed to greater oxidative stress than control scalps, possibly resultant from increased respiratory chain activity 9, 10. Increased levels of GPX4 would also protect the increased amount of lipid synthesized in the patient vertex scalp from phospholipid hydroperoxides-mediated oxidation
What we can gather here is the major mechanism of Androgenetic Alopecia is an involvement of Cholesterol and the resulting downstream mechanisms(sex hormones and even downstream lipids like prostaglandins and leukotrienes)
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