Exploring The Hormonal Route. Hair=life.

[Experimentality]

Dug up some cool research on prolactin (PRL) and its effects on scalp hair loss.

Calcineurin upregulates PRL receptor expression in human HFs

We already knew that our old friend Cyclosporine A inhibits calcineurin, and thereby potently upregulates stem cell (SC) differentiation. From the article:

One key regulator of SC activity in the HF is the transcription factor nuclear factor of activated T cells c1 (Nfatc1), which is expressed in bulge SCs (Tumbar et al. 2004; Rhee et al. 2006; Horsley et al. 2008). Nfatc1 activity is directly regulated by the phosphatase calcineurin (CN), which dephosphorylates Nfatc1 to induce its nuclear translocation and transcriptional activity (Rao et al. 1997; Horsley and Pavlath 2002). Inactivation of Nfatc1 through skin-specific genetic knockout or treatment with cyclosporine A (CSA), an inhibitor of CN (Mattila et al. 1990), results in precocious activation of HF growth in mice (Paus et al. 1989; Gafter-Gvili et al. 2003; Horsley et al. 2008).

Then, the study continues to identify a previously unknown relation to prolactin:

In this study, we identified genetic changes associated with SC activation following administration of CSA, a robust activator of follicular SCs. Gene expression profiling revealed a novel molecular interplay between Nfatc1 and Prlr, implicating Prl signaling as a regulator of SC activity in the hair. Using pharmacological and genetic experiments in mice, we revealed that Prl signaling and Nfatc1 expression are required for the abrogation of hair growth during pregnancy. Furthermore, we demonstrated that direct administration of Prl promotes HF quiescence. Finally, we showed that Prl signaling activates Jak/Stat5 signaling in follicular SCs to maintain their dormancy. Our findings unveil a novel CN–Nfatc1–Prlr–Stat5 pathway that governs skin SC quiescence downstream from a systemic hormone.

In simpler terms, calcineurin is at the start of this CN-Nfatc1-PRL-Stat5 axis. Thus, CN upregulates PRL receptor density, whereas Cyclosporine A directly kills the entire pathway. So far, CsA is the only compound that I ran across that directly downregulates PRL receptors. The study also continues to show that PRL, and by extension Stat5 induces "SC quiescence", which is the same as shortening anagen/inducing catagen in HFs (which we already knew). More on the catagen inducing effects of PRL can be read here, among others.

More studies then. Bad news for E2 (and thyrotropin).

E2 increases PRL secretion and PRL receptor density in HFs

Oestrogen treatment significantly upregulated PRL and PRLR immunoreactivity in selected skin and hair follicle compartments, at the gene and protein level (P < 0.05).

This was at concentrations of 100nM, which can be achieved by a 1mcg/mL E2 topical. It is unknown what concentrations are achieved with oral/transdermal full HRT, because serum concentrations do not necessarily correspond to scalp concentrations. Of course, the positive effects of E2 will (massively) override the negative effects it has on PRL secretion (as shown in other papers mentioned in other posts of mine), but still it is something to be aware of. PRL should ideally be reduced (and receptors be blocked to prevent upregulation).

In conclusion, PRL receptor density is downregulated by CsA, but it is not a PRL receptor antagonist (so far, only the experimental antibody is). CsA increases SC differentiation and promotes anagen. It is unknown if other CN inhibitors like Tacrolimus can promote anagen to a similar extent as CsA, but they should all be able to potently downregulate PRL receptor density. Safety concerns aside, this makes them interesting compounds to consider for topical hairloss formulations (apart from its PRLr downregulating effect, CsA also inhibits sFRP1 (inducing the Wnt pathway) and inhibits several interleukins (ILs), thereby directly increasing SC differentiation and suppressing inflammitory responses).

 

[Gergely]

Slow but steady progress

 

[Almas_NW0]

View attachment 170084
Slow but steady progress

nw0 hairline?
You seem to be returning to your original growth line.
Has injections accelerated your progress?

 

[MylovelyHair]

View attachment 170084
Slow but steady progress

can you show us crown too??

 

[finastride23]

Valerate and semihydrate (E2) are bioidentical estrogens, well tolerated and accepted by the body and have fewer side effects than ethinyl estradiol (EE).
I've taken both drugs, and if I had to choose, I'd prefer the half-hydrate - its molecular weight is less and it's more suitable for sublingual administration.
I've never taken EE and I don't recommend that crap to anyone.

why don’t you recommend EE?

 

[Get my hair back]

why don’t you recommend EE?

If you take EE without E2/E3 support, the cup tilts toward stimulation of the ER-alpha receptor, which can cause premature catagen of the hair follicles.
It can be used in combination therapy where E2/E3 will dominate.
But I do not advise to take ethinyl estradiol, it is a bad estrogen with a high risk of venous thrombosis.

 

[finastride23]

is estradiol valert good for hair?

 

[Get my hair back]

is estradiol valert good for hair?

Yes. I got my first results on valerate.

 

[Gergely]

Has injections accelerated your progress?

No not really, it was minoxidil

 

[Almas_NW0]

No not really, it was minoxidil

Oral? Minoxidil must be helpful when follicles are hard to bring back to life. My hair is now growing back along the Norwood 0 line, so I'll do without it

 

[Pls_NW-1]

Cant believe that I have even thinning on my sides, like... my whole head hair LOL

 

[MylovelyHair]

Are you sure this is male pattern baldness ??

 

[Pls_NW-1]

Are you sure this is male pattern baldness ??

My hairline is slowly going away and my crown is barebone, almost gone.

I was thinking about wearing a hair system, but now even the sides and back... oof.

Dunno what to do. Just want to have great hair

 

[MrSnow]

My hairline is slowly going away and my crown is barebone, almost gone.

I was thinking about wearing a hair system, but now even the sides and back... oof.

Dunno what to do. Just want to have great hair

mikasa, which product for you hair do you use ?

 

[Pls_NW-1]

mikasa, which product for you hair do you use ?

I do like Mikasa, but my name is Sasha Braus.

Cannot use medications, the doctor said. Due to having an inexplicable hormonal imbalance.

Letting it go and probably just forgetting about it, my meat is more important to me, Sasha said.

Goddes bless, holy Ymir!

 

[Solxama]

OMG, I feel for you @Pls_NW-1 , that hair situation and so much health problems at your young age must be really challenging for you. I thought I had it bad with balding starting at 17 and my demanding skin, but at least I can treat it as I have nothing standing in the way health wise.

I tried accepting hair loss, but in my situation it was impossible, I hope you find it easier if it's your only choice, but still I hope your hair and health situation gets better at some point. Miracles do happen, I thought my mum would never get better, but she did after finding good treatment and doctors after years of neglect from most local medical professionals.

 

[Gergely]

Oral? Minoxidil must be helpful when follicles are hard to bring back to life. My hair is now growing back along the Norwood 0 line, so I'll do without it

Topical 5% i wouldn't want to grow hair on my back

can you show us crown too??

 

[Get my hair back]

View attachment 170117View attachment 170118
Cant believe that I have even thinning on my sides, like... my whole head hair LOL

Buddy, you have diffuse alopecia.

 

[KNemo]

I do like Mikasa, but my name is Sasha Braus.

Cannot use medications, the doctor said. Due to having an inexplicable hormonal imbalance.

Letting it go and probably just forgetting about it, my meat is more important to me, Sasha said.

Goddes bless, holy Ymir!

Maybe you should get a second/third opinion?

 

[Pls_NW-1]

Maybe you should get a second/third opinion?

Well this was a sixth opinion from a good endocrinologist. I currently am now in treatment