Samumed sm04554. Only drug on phase 3
- Thread starter wow-wow
- Start date
Balides are desperate and would do anything for hair. We would drink acid straight from the tubes if that meant new hairs would sprout on top of our heads.
You can bet that if a bald man doesn't stick with a treatment it is only because it doesn't f*cking work. We may all be bald mofos here but not everyone is a delusional fool forever.
You can bet that if a bald man doesn't stick with a treatment it is only because it doesn't f*cking work. We may all be bald mofos here but not everyone is a delusional fool forever.
Last edited:
If it grows just one hair it works. Combine with 99 other things that grow one hair and you have 100 new hairs.
lol ok
I didn't mean that literally, obviously you didn't get the point.
- Reaction score
- 637
Does anyone know the exact mechanism for how DHT causes miniaturization? It’s said that it builds up on the follicle and causes damage to the hair cycle. But why does the build up do that? Is that build up inflammatory or is it as simple as a physical blockade? What’s the nature of the build up and why does it interact with hair follicles in this way?
It's not that it builds up on the follicle and damages it directly. When androgens bind to the AR they signal some genes to turn on and others to turn off. High levels of AR expression stress this downstream system, and gene expression becomes dysregulated. It's incredibly complex. It's easy to shut off the AR with AR antagonists or 5-ARIs which saves the hair you have left, but restoring homeostasis to the dozens of genetic factors involved downstream is very difficult. It's not even fully understood yet how the different pathways work together to create hair and keep it cycling. The most significant is a broken Wnt pathway, so Samumed and others are focused on restoring that.
- Reaction score
- 637
That does seem more complex than I thought. I had assumed it was scar tissue or fibrosis that was causing lack of regrowth. But there seems to be a cascade of pathways affected semi permanently by balding.
If estrogen is really the only super effective growth agonist that people have used, shouldn’t it be studied? Somehow estrogen affects the pathways involved in the downstream effects of androgen expression, reversing the balding. If we have data for the pathways affected by androgens and then we look at the data of those suspected pathways affected by estrogen, we can look at the intersection/differentials.
Maybe that’s the key
That's exactly right. I'm sure researchers have looked into it for answers, but there aren't very many researchers in this field. I think it was @InBeforeTheCure who posted the genes upregulated and downregulated by estrogen somewhere on this forum if you want to have a look, and cross-reference them with the genes upregulated and downregulated in Androgenetic Alopecia.
- Reaction score
- 637
Thank you. I’ll look into it, maybe I can get somewhere.
Plan of action: gather data of genes up regulated/downregulated in balding men in Androgenic Dataset. Cross reference those genes against estrogenic regulation which is stored in an Estrogen Dataset, ie the criteria is filled if a gene is shared across both datasets but the regulation goes in opposite directions.
Make final list of genes that meet the criteria. Research pathways involved.
Last edited:
- Reaction score
- 950
@Selb
E2 upregulates these genes:
E2 downregulates these genes:
Source is Conrad et al.. They tested only 1300 genes.
An important example: Hedgehog target genes in human keratinocytes are significantly enriched among the E2 target genes.
E2 upregulates these genes:
Code:
Gene Fold.Change
FLNA 2.18
COMP 2.16
KRT19 1.92
KRT2 1.92
TAGLN 1.87
SRRM2 1.86
KRT75 1.85
LAMA5 1.76
PDLIM7 1.73
KRT37 1.73
KRT17 1.7
NKTR 1.64
MAGEA11 1.63
COL18A1 1.61
PMEL 1.57
ATP5D 1.56
ACTB 1.56
KRT14 1.55
COL6A2 1.54
CSPG4 1.54
MAP2K2 1.52
PTK7 1.52
GSTP1 1.52
CCND1 1.52
ERCC2 1.52
NFATC4 1.51
COL11A1 1.51
COL16A1 1.49
TKT 1.49
PPP1R13L 1.49
FOSL2 1.48
NDUFA3 1.47
KRT5 1.46
BASP1 1.44
MGP 1.43
EGFR 1.42E2 downregulates these genes:
Code:
Gene Fold.Change
MMP3 0.18
FLG 0.2
MMP1 0.32
SPP1 0.33
JAK1 0.35
FN1 0.36
ITGAV 0.37
SOD2 0.38
FGFR2 0.39
CDKN2B 0.4
GLRX 0.41
HACL1 0.41
AIM1 0.42
COL12A1 0.42
CDH1 0.43
CDKN1A 0.43
DCN 0.43
S100A9 0.44
SPRR2D 0.44
EPS8 0.44
HK2 0.45
CD36 0.45
S100A7 0.46
SPRR1A 0.46
SOCS5 0.46
NOV 0.47
LCN2 0.48
SPARCL1 0.48
MCL1 0.49
SDCBP 0.5
GJA1 0.5
TDG 0.5
CANX 0.5
CASP2 0.5
NID1 0.51
SERPINE1 0.51
IL1A 0.51
EDNRB 0.52
PTGDS 0.52
TNFRSF19 0.52
TXLNA 0.52
CCNG2 0.53
DSC1 0.53
ITGA6 0.53
CXCL1 0.53
IQGAP1 0.54
ITGB6 0.54
PDLIM5 0.54
MAPK14 0.54
DDX3X 0.55
EMP1 0.55
UBQLN1 0.56
TJP2 0.56
IL6 0.56
PLIN2 0.56
RAF1 0.56
EPS15 0.57
ITGA2 0.57
PPIL4 0.57
CALR 0.57
CCT8 0.57
EIF4H 0.58
ADAM9 0.58
ABCC5 0.58
MAPK6 0.59
SEC31A 0.59
HIF1A 0.6
GLUL 0.6
FOS 0.6
STAT2 0.6
STAT1 0.6
CCT4 0.6
FCGR1A 0.6
FMOD 0.61
VCAN 0.61
BCL2L13 0.62
COL6A3 0.62
THBS2 0.62
UNG 0.62
VEGFA 0.62
THBS1 0.62
LTBP1 0.62
ASAH1 0.62
GCLC 0.62
TNFRSF1A 0.62
CCNC 0.63
KRT38 0.63
MAPK1 0.63
CLU 0.63
IGFBP3 0.63
CD55 0.63
MCC 0.63
CASP8 0.63
HSPD1 0.64
S100A8 0.64
CORO1C 0.64
CDH5 0.64
TFDP1 0.64
DNAJA3 0.64
ERO1A 0.65
ABCB6 0.65
CD44 0.65
CGA 0.65
LUM 0.65
CDKN1B 0.65
PSAP 0.65
TGFA 0.65
CASP7 0.65
HADHB 0.65
GLIPR1 0.65
MFAP3 0.65
BCL10 0.65
PTK2 0.65
KRT1 0.65
CD34 0.66
ACOX1 0.66
VHL 0.67
EIF3E 0.67
BCL2L2 0.67
PSEN1 0.67
TNFSF10 0.67
LDLR 0.67
RIPK1 0.67
KRT36 0.67
PIM1 0.68
GJB2 0.68
B2M 0.68
LAMA4 0.68
XRCC5 0.68
CPE 0.68
HOPX 0.69
P4HB 0.69
PRKCH 0.69
LGALS8 0.69
MFAP5 0.69
VBP1 0.69
BCL2L1 0.69
ITGB1 0.7
CWC27 0.7
TP53 0.7
CTNNB1 0.7
MCM5 0.7
PDZK1IP1 0.7Source is Conrad et al.. They tested only 1300 genes.
An important example: Hedgehog target genes in human keratinocytes are significantly enriched among the E2 target genes.
- Reaction score
- 637
Thanks, this is super helpful
- Reaction score
- 69
Does that apply to all estrogens or just e2?
- Reaction score
- 950
They tested only E2. I don't know what we could extrapolate to other estrogens.
- Reaction score
- 197
I personally think its both issues as Balding men in autopsies have densly calcified scalps, where as non balding men had significantly less calcium build up. Also, as we grow older our scalp stretches out and thins out (thinning could be due to highly androgenic DHT); our brains demand a crazy amount of blood flow and nutrients as well, taking away from other areas of our body.
However; DHT is the predominant culprit here. There are many compunding factors such as growth of scalp, thinning of skin, blood flow, gene transcription and pathway signaling, Cellular Metabolism, AR density etc... DHT literally causes calcification and scar tissue build up at the site of injured / damaged tissue in all areas of the body that ive studied; I dont see why it would be any different in the scalp...
- Reaction score
- 453
No sides effects? Really?
If anything it would probably have a positive effect on collagen production if its action is limited to Wnts.
- Reaction score
- 637
If you also have on hand a good list of upregulated/downregulated genes for AA, that would be helpful. They don't need to have too many common genes in the estrogen dataset. I have a list already but it seems a bit short.