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your question is a good question.
the answer is no, because the cholesterol is not the 1 that grows hair. It's cholesterol's end-products that are growing hair- which is progesterone and estradiol(and calcitriol in some people)- for these are the terminal products of activated hedgehog signalling- which is immediately downstream of Gli2- the terminal effector of Hedgheog signalling.
i have tried topical cholesterol- it makes scalp itch and pain worst. IMO, it's very likely the cholesterol just gets metabolized into more androgens in the scalp.
It's the kind of cholesterol-derived product that we are looking at- not cholesterol itself
Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development.
Mill P1, Mo R, Fu H, Grachtchouk M, Kim PC, Dlugosz AA, Hui CC.
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Abstract
Sonic hedgehog (Shh) signaling plays a critical role in hair follicle development and skin cancer, but how it controls these processes remains unclear. Of the three Gli transcription factors involved in transducing Shh signals in vertebrates, we demonstrate here that Gli2 is the key mediator of Shh responses in skin. Similar to Shh(-/-) mice, Gli2(-/-) mutants exhibit an arrest in hair follicle development with reduced cell proliferation and Shh-responsive gene expression, but grossly normal epidermal differentiation. By transgenic rescue experiments, we show that epidermal Gli2 function alone is sufficient to restore hair follicle development in Gli2(-/-) skin. Furthermore, only a constitutively active form of Gli2, but not wild-type Gli2, can activate Shh-responsive gene expression and promote cell proliferation in Shh(-/-) skin. These observations indicate that Shh-dependent Gli2 activator function in the epidermis is essential for hair follicle development. Our data also reveal that Gli2 mediates the mitogenic effects of Shh by transcriptional activation of cyclin D1 and cyclin D2 in the developing hair follicles. Together, our results suggest that Shh-dependent Gli2 activation plays a critical role in epithelial homeostasis by promoting proliferation through the transcriptional control of cell cycle regulators.
GLI2 Is Expressed in Normal Human Epidermis and BCC and Induces GLI1 Expression by Binding to its Promoter
Author links open overlay panelMohammed S.Ikram*Graham W.Neill*GerhardRegl†ThomasEichberger†Anna-MariaFrischauf†FritzAberger†AnthonyQuinn*MikePhilpott*
https://doi.org/10.1111/j.0022-202X.2004.22612.xGet rights and content
Under an Elsevier user license
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Sonic hedgehog (Shh) binds to its receptor patched (PTCH), leading to the activation and repression of target genes via the GLI family of zinc-finger transcription factors. Deregulation of the Shh pathway is associated with basal cell carcinoma (BCC) due to upregulation of GLI1 and GLI2. We recently demonstrated a positive feedback loop between GLI1 and GLI2, which revealed that GLI1 may be a direct target of GLI2. Using band shift and luciferase reporter assays, we now show that GLI2 binds the GLI-binding consensus sequence in the GLI1 promoter. These data suggest that GLI2 directly activates GLI1 and that retrovirally expressed GLI2 induces expression of endogenous GLI1 in human primary keratinocytes. Finally, using in situ hybridization, we show that GLI2 is expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumor islands. These results suggest an important role for GLI2 in regulating epidermal proliferation and skin tumorigenesis.
I highly recommend you to peruse just this study- https://www.ncbi.nlm.nih.gov/pubmed/25582983.
Remember https://www.genecards.org/cgi-bin/carddisp.pl?gene=GLI2 is the 1 that grows hair
It is strongly implied Progesterone is defnitely missing in alopecic scalp. This list of pathways downregulated in alopecic scalp from the primero study in this thread implies it:
Hedgehog signaling pathway
Progesterone-mediated oocyte maturation
Oocyte meiosis SNARE interactions in vesicular transport
Phospholipase D signaling pathway
Maturity onset diabetes of the young
Description of the Progesterone-mediated oocyte maturation pathway:
http://www.genome.jp/kegg-bin/show_pathway?map=xla04914&show_description=show
"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."
Coupled by the fact that Progesterone is coincidentally, indeed the product of activated Hedgheog signalling as discovered by another study(and it's a DHT-inhibitor as well) - all these strongly backs up the implication of progesterone as being the key hormone missing in alopecic scalp. In fact, u just have to read Progesterone's wiki entry to be able to see why it helps grow hair.
IGF-1/Insulin is not the missing gene in alopecic scalp- they are in fact, the causative pathways of Androgenetic Alopecia(go dig for numerous studies all indicating that IGF-1 is overexpressed in vertex scalp of balding men)
The 2nd study in this thread already indicated that the Insulin receptor is overexpressed in alopecic tissue. This means our balding scalps are highly sensitive to Insulin/Igf-1(igf-1 can bind to the Insulin receptor )- the fact that sebocytes are enlarged there highlights this phenomenon.
THis recent sutdy from feb 2018 again reinforces this observation:
Article Prostaglandin D2-Mediated DP2 and AKT Signal Regulate the Activation of Androgen Receptors in Human Dermal Papilla Cells
Abstract: Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2)(aka CRTh2) is known to be an important factor in androgenetic alopecia (Androgenetic Alopecia). However, the effect of PGD2 in human dermal papilla cells (hDPCs) is not fully understood. The function of PGD2-induced expression of the androgen receptor (AR), DP2, and AKT (protein kinase B) signal were examined by using real time-PCR (qRT-PCR), western blot analysis, immunocytochemistry (ICC), and siRNA transfection system. PGD2 stimulated AR expression and AKT signaling through DP2. PGD2 stimulated AR related factors (transforming growth factor beta 1 (TGFβ1), Creb, lymphoid enhancer binding factor 1 (LEF1), and insulin-like growth factor 1, (IGF-1)) and AKT signaling (GSK3β and Creb) on the AR expression in hDPCs. However, these factors were down-regulated by DP2 antagonist (TM30089) and AKT inhibitor (LY294002)(and Setipiprant) as well as DP2 knockdown in hDPCs decreased AR expression and AKT signaling. Finally, we confirmed that PGD2 stimulates the expression of AR related target genes, and that AKT and its downstream substrates are involved in AR expression on hDPCs. Taken together, our data suggest that PGD2 promotes AR and AKT signal via DP2 in hDPCs, thus, PGD2 and DP2 signal plays a critical role in AR expression. These findings support the additional explanation for the development of Androgenetic Alopecia involving PGD2-DP2 in hDPCs.
IGF-1, which are related to the activity of AR and AKT signalling, was blocked by TM30089(same drug class as Setipiprant) (Figure 4D–G). In addition, protein levels of AR and phosphorylation of AKT/GSK3β was also reduced by the TM30089. (Figure 4H). PGD2-inhibited cell viability was significantly recovered by 30% upon treatment with TM30089 compared with the PGD2-treated group (Figure 4I). These results indicated that AR expression and hDPC viability were regulated by PGD2 through DP2. Figure 3. PGD2 regulates the AKT signal. The AKT phosphorylation was determined using western blot analysis. hDPCs were treated with PGD2 (200 nM) for the indicated times and harvested (A). hDPCs were pretreated with LY294002 for 1 h, and then PGD2 (200 nM) treatment for 5 h. The protein levels of AR, and AKT/GSK3β/Creb phosphorylation was measured using western blot analysis (B). The mRNA expression of AR, LEF1, Creb, and IGF-1 was measured using qRT-PCR (C). β-actin served as a loading control for protein normalization. GAPDH was used as an internal control for mRNA normalization. The results are expressed as the mean ± SD of three independent experiments. * p < 0.05, compared with the control (0 nM PGD2), # p < 0.05 compared with PGD2. 2.4. PGD2-Induced AR Expression and AKT Signalling Are Regulated by a DP2 Antagonist We confirmed that PGD2-DP2 affects AR expression via AKT and its involved factors (including LEF1, Creb, and IGF-1). We hypothesized that suppression of DP2 would inactivate AR expression by inhibiting AR-related factors and AKT signalling. Thus, we examined whether inhibition of DP2 could regulate the activity of AR and its related factors. TM30089 has been known as a highly potent antagonist on mouse CRTH2/DP2 [10]. PGD2-induced AR, DP2, and COX2 mRNA expression was reduced by TM30089 (Figure 4A–C). We also found that the mRNA expression of TGFβ1, Creb, LEF1, and IGF-1, which are related to the activity of AR and AKT signalling, was blocked by TM30089 (Figure 4D–G). In addition, protein levels of AR and phosphorylation of AKT/GSK3β was also reduced by the TM30089. (Figure 4H). PGD2-inhibited cell viability was significantly recovered by 30% upon treatment with TM30089 compared with the PGD2-treated group (Figure 4I). These results indicated that AR expression and hDPC viability were regulated by PGD2 through DP2.
= PGD2 ups IGF-1 via CRTh2
In fact, the man whose team discovered that PGD2 is upregulated inbalding scalps already clearly listed IGF-1 as being overexpressed- in balding scalp:
https://patents.google.com/patent/US20110021599A1/en Page 91, the 21st most upregulated gene in alopecic scalp.
IGF-1/insulin growths facial/body hair- but not scalp hair in balding men. It puts bullshit snake oil products like this http://www.jhgc.com.sg/theory/igf-1/index.html to shame.
IGF-1/Insulin grows scalp hair in balding scalps? Your call- though i say they defnitely grow muscles and beards(and an oily face)
If as simple as estrogen and progesterone in scalp, why is no one using this? Very cheap from online sources. Apply topically. Get blood test before, and seven days after. Take aromatase inhibitor to equalize estrogen levels.
