Bayer Prolactin Receptor Antibody For Male And Female Pattern Hair Loss

[jan_miezda]

Relevant article from 2020

https://res.mdpi.com/d_attachment/ijms/ijms-21-05342/article_deploy/ijms-21-05342.pdf

The mechanism whereby prolactin directly regulates hair growth is connected with its inhibitory influence on hair shaft elongation and the premature induction of the catagen phase (causes miniaturization). Moreover, luteotropin (Prolactin) also plays a significant role in the proliferation and apoptosis of keratinocytes in HFs by decreasing the number of Ki-67-positive cells and increasing the quantity of TUNEL + cells [18]. Prolactin is recognized as an androgen metabolism modulator. The luteotropic hormone seems to increase the level of free testosterone and dehydroepiandrosterone sulfate, decreasing at the same time the level of serum testosterone-estradiol-binding globulin [24,25]. PRL also appears to inhibit the activity of 5-alpha

this is interesting beacause it mentions a prolactin receptor on the outer root sheath region of the hair follicle. There can be a lot of pharmaceutical approaches for blocking its activity. But this is hard because the external root sheath is inside a glossy membrane. It will be hard for the molecule to interact with that receptor. It also says prolactin inhibits 5ar activity.I know in men and women prolactin causes increased expression of estrogen receptors this can be a good reason why miniaturization is much slower in women:

“The ability of the rat corpus luteum to respond to estrogen requires prolactin (PRL), which can stimulate the expression of the estrogen receptor (ER).”

Prolactin regulation of estrogen receptor expression - PubMed

The ability of the rat corpus luteum to respond to estrogen requires prolactin (PRL), which can stimulate the expression of the estrogen receptor (ER). This review will focus on the signaling mechanisms by which this occurs. Transcription of the genes encoding both ERalpha (Esr1) and ERbeta...

pubmed.ncbi.nlm.nih.gov

 

[jan_miezda]

Prolactin receptor expression is also closely tied to serum GH. This study shows for group B (20-40 years old) as GH receptor expression declines PRLC expression increases. This can be why younger kids dont experience hair loss. As we age IGF - receptor reactivity in hair follicles declines in balding people.

Growth hormone (GH) and prolactin receptors in human peripheral blood mononuclear cells: relation with age and GH-binding protein - PubMed

GH receptors (GHRs) and PRL receptors (PRLRs) were studied in human peripheral blood mononuclear cells (PBMC) using flow cytometry, biotinylated anti-GH receptor monoclonal antibody 10B8, and biotinylated human PRL. Variations of GHR and PRLR expression and the relationship of plasma GHBP and GH...

pubmed.ncbi.nlm.nih.gov

 

[czecha]

"Prolactin acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects."
Clapp, C., Thebault, S., Macotela, Y., Moreno-Carranza, B., Triebel, J., & Martinez de la Escalera, G. (2015). Regulation of blood vessels by prolactin and vasoinhibins. Adv Exp Med Biol, 846, 83-95. doi:10.1007/978-3-319-12114-7_4

Vasoinhibins: a family of N-terminal prolactin fragments that inhibit angiogenesis and vascular function - PubMed

Antiangiogenic molecules derived from prolactin (PRL) are not a single entity, but rather a family of peptides with different molecular masses, all containing the N-terminal region of PRL. Cleavage of PRL by cathepsin-D or by matrix metalloproteases generates N-terminal fragments that act on...

pubmed.ncbi.nlm.nih.gov

 

[coolio]

Prolactin receptor expression is also closely tied to serum GH. This study shows for group B (20-40 years old) as GH receptor expression declines PRLC expression increases. This can be why younger kids dont experience hair loss. As we age IGF - receptor reactivity in hair follicles declines in balding people.

Definitely interesting.

 

[RolfLeeBuckler]

Who is able to translate the timelinie of HMI-115? It looks like they do Phase II/ Phase II in one round

肖瑞平：打通转化医学的最后一公里_药智新闻

肖瑞平已在转化医学领域耕耘多年，她也属于转化医学先行者之一。

news.yaozh.com

 

[trialAcc]

Who is able to translate the timelinie of HMI-115? It looks like they do Phase II/ Phase II in one round

View attachment 160022

肖瑞平：打通转化医学的最后一公里_药智新闻

肖瑞平已在转化医学领域耕耘多年，她也属于转化医学先行者之一。

news.yaozh.com

Lots of companies do this, it just means the trial will probably have an extension set of phase 3 outcomes if the primary phase 2 outcomes measurements are met during the trial. Similarly a phase 1/2 trial will have phase 1 end points that are usually largely based on safety with some phase 2 end points of effectiveness.

 

[Tom4362]

Who is able to translate the timelinie of HMI-115? It looks like they do Phase II/ Phase II in one round

View attachment 160022

肖瑞平：打通转化医学的最后一公里_药智新闻

肖瑞平已在转化医学领域耕耘多年，她也属于转化医学先行者之一。

news.yaozh.com

(online translation)

 

[RolfLeeBuckler]

(online translation)

thank you! what is the name of the program you use for image translation?

 

[Tom4362]

thank you! what is the name of the program you use for image translation?

Look up 'image translation' on Google, you will probably find better ones than the one I used

 

[Kagaho]

The macaque study evidence is promising, undoubtely. But with human Androgenetic Alopecia fucked up stem cells (premature scenescence) play a big role. Its going to be a new powerful weapon, but to think this thing its going to reverse balding mmm.

 

[pegasus2]

The macaque study evidence is promising, undoubtely. But with human Androgenetic Alopecia fucked up stem cells (premature scenescence) play a big role. Its going to be a new powerful weapon, but to think this thing its going to reverse balding mmm.

PRL keeps hair follicle stem cells in a quiescent state, so hmmmm

 

[Norwood-null-by-2021]

Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro - PubMed

Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3...

pubmed.ncbi.nlm.nih.gov

 

[RolfLeeBuckler]

Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro - PubMed

Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3...

pubmed.ncbi.nlm.nih.gov

what is your conlusion out of this article?

 

[whatevr]

what is your conlusion out of this article?

He thinks that this disproves prolactin signalling inhibition being helpful for Androgenetic Alopecia because retinoic acid already does it and isn't very helpful.

Too bad that's not how any of this works.

 

[pegasus2]

It's not even a good attempt to dismiss HMI. He's just hoping no one will even read the study he posted, and it proves he's just trolling.


"no change in the stability of prolactin receptor mRNA was observed during 12 h of retinoic acid treatment"

 

[pegasus2]

Pax1 and RUNX2 are possible downstream targets of prolactin. Antagonizing the PRLR downregulates Pax1 and upregulates RUNX2. There should be a good synergistic effect with Wnt agonists like KY19382 or VPA.

Pax1 and other Pax genes are strongly upregulated by prolactin. Pax1 is the gene with the greatest association with Androgenetic Alopecia after the androgen receptor. You can check your Androgenetic Alopecia risk on three of the Pax1 SNPs here. This is a tumor suppressor gene(anti-proliferative). It likely acts to shut down cell proliferation in the HF as if it were a tumor.

Primary SNP:

PAX1 rs2180439 [R, R]

• ‘C’ = Higher odds of male-pattern baldness, relative to ‘T’
• ‘T’ = Lower odds of male-pattern baldness, relative to ‘C’

Other Important SNPs:

PAX1 rs1160312 [R]

• ‘A’ = Higher odds of male-pattern baldness, relative to ‘G’
• ‘G’ = Lower odds of male-pattern baldness, relative to ‘A’

PAX1 rs6047844 [R]

• ‘T’ = Higher odds of male-pattern baldness, relative to ‘C’
• ‘C’ = Lower odds of male-pattern baldness, relative to ‘T’

Cobb found the second strongest association with male pattern baldness from the 20p11 region between PAX1 encoding paired box protein 1 and FOXA2 encoding forkhead box protein A2

Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

Androgenetic alopecia, known in men as male pattern baldness (male pattern baldness), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies ...

www.ncbi.nlm.nih.gov

The results showed that PAX1 was expressed at very high levels in the scalp skin. Although the PAX1 gene is more than 100 kb away from the 20p11–associated LD block, the expression data might suggest that PAX1 confers the Androgenetic Alopecia-relevant effect at this locus and that a regulatory variant within the associated LD block may modulate its expression through long-range control.

Genetic Variants at 20p11 Confer Risk to Androgenetic Alopecia in the Chinese Han Population

Androgenetic alopecia (Androgenetic Alopecia) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, ...

www.ncbi.nlm.nih.gov

On the other side of the coin prolactin has been shown to downregulate RUNX2, a protein that is important for stem cell differentiation and has a synergistic relationship with Wnt signaling. The RUNX family of genes is also closely associated with A.G.A.

Osteoblasts exposed for 48 h to 1000 ng/mL PRL, but not to 10 or 100 ng/mL PRL, showed decreases in the mRNA expression of Runx2, osteoprotegerin (OPG), and receptor activator of nuclear factor kappaBeta ligand (RANKL) by 60.49%, 72.74%, and 87.51%

Prolactin decreases expression of Runx2, osteoprotegerin, and RANKL in primary osteoblasts derived from tibiae of adult female rats - PubMed

Hyperprolactinemia caused by physiological or pathological conditions, such as those occurring during lactation and prolactinoma, respectively, results in progressive osteopenia. The underlying mechanisms, however, are controversial. Prolactin (PRL) may directly attenuate the functions of...

pubmed.ncbi.nlm.nih.gov

 

[Dimitri001]

Pax1 and RUNX2 are possible downstream effectors of prolactin's regulation of hair growth. Antagonizing the PRLR downregulates Pax1 and upregulates RUNX2. There should be a good synergistic effect with Wnt agonists like KY19382 or VPA.

Pax1 and other Pax genes are strongly upregulated by prolactin. Pax1 is the gene with the greatest association with Androgenetic Alopecia after the androgen receptor. You can check your Androgenetic Alopecia risk on three of the Pax1 SNPs here. This is a tumor suppressor gene(anti-proliferative). It likely acts to shut down cell proliferation in the HF as if it were a tumor.

Primary SNP:

PAX1 rs2180439 [R, R]

• ‘C’ = Higher odds of male-pattern baldness, relative to ‘T’
• ‘T’ = Lower odds of male-pattern baldness, relative to ‘C’

Other Important SNPs:

PAX1 rs1160312 [R]

• ‘A’ = Higher odds of male-pattern baldness, relative to ‘G’
• ‘G’ = Lower odds of male-pattern baldness, relative to ‘A’

PAX1 rs6047844 [R]

• ‘T’ = Higher odds of male-pattern baldness, relative to ‘C’
• ‘C’ = Lower odds of male-pattern baldness, relative to ‘T’

Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness

Androgenetic alopecia, known in men as male pattern baldness (male pattern baldness), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies ...

www.ncbi.nlm.nih.gov

Genetic Variants at 20p11 Confer Risk to Androgenetic Alopecia in the Chinese Han Population

Androgenetic alopecia (Androgenetic Alopecia) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, ...

www.ncbi.nlm.nih.gov

On the other side of the coin prolactin has been shown to downregulate RUNX2, a protein that is important for stem cell differentiation and has a synergistic relationship with Wnt signaling. The RUNX family of genes is also closely associated with A.G.A.

Prolactin decreases expression of Runx2, osteoprotegerin, and RANKL in primary osteoblasts derived from tibiae of adult female rats - PubMed

Hyperprolactinemia caused by physiological or pathological conditions, such as those occurring during lactation and prolactinoma, respectively, results in progressive osteopenia. The underlying mechanisms, however, are controversial. Prolactin (PRL) may directly attenuate the functions of...

pubmed.ncbi.nlm.nih.gov

If we downregulate a tumor suppressing gene systemically, is that a concern?

 

[pegasus2]

If we downregulate a tumor suppressing gene systemically, is that a concern?

I don't think so because BAY doesn't directly antagonize it, it only antagonizes one thing that is theoretically upregulating it in the hair follicle. It can still be activated by other processes. Also prolactin is normally proliferative and Pax1 is probably upregulated as a negative feedback regulator. Inhibiting prolactin is a treatment for brain tumors, prostate cancer, and best cancer. It would theoretically reduce your risk of cancer

 

[pegasus2]

This image shows the expression of several hair growth genes in mesenchymal cells of RUNX2- mice. GLI1, FGFR2, TCF7, and Wnt10b are virtually eliminated when RUNX2 is downregulated.

Runx2 regulates cranial suture closure by inducing hedgehog, Fgf, Wnt and Pthlh signaling pathway gene expressions in suture mesenchymal cells - PubMed

Cleidocranial dysplasia (CCD, #119600), which is characterized by hypoplastic clavicles, open fontanelles, supernumerary teeth and a short stature, is caused by heterozygous mutations in RUNX2. However, it currently remains unclear why suture closure is severely impaired in CCD patients. The...

pubmed.ncbi.nlm.nih.gov

Here is a review on prolactin's regulation of stem/progenitor cells, with a little bit about prolactin in the hair follicle.

Minireview: Prolactin Regulation of Adult Stem Cells

Adult stem/progenitor cells are found in many tissues, where their primary role is to maintain homeostasis. Recent studies have evaluated the regulation of adult stem/progenitor cells by prolactin in various target tissues or cell types, including the ...

www.ncbi.nlm.nih.gov

 

[RolfLeeBuckler]