Isotretinoin and FOX01

#1

acne.org/messageboard/post-a37337-.html

#2

?

#3

You don’t understand the article ?

#4

I barely read it, can you break it down? why is it relevant?

#5

Sure, it’s saying that FOXO transcription factors are crucial regulatory proteins:

In a nutshell, isotretinoin fiddles with the aforementioned transcription factors to the detriment of the patient on the poison.

#6

This section of the study really caught my eye: “Isotretinoin, FoxO1 and Suppression
of Androgen Receptor Transactivation”

There was another section that discussed how it could effect the limbic system. (possible cause of emotional blunting?)

Thank you very much for posting this notworthit.

#7

Yes, I stumbed upon it over at acne. org. I might take it down though, because I think it irks some members. I think I am still being quizzed on it.

#8

I am not irked on it at all, i just struggled to understand it that’s all. Keep extracting what you can from it.

#9

Pull the other one: it’s all there in the subheading for all to see. All we talk about here is suppression of the androgen receptor (not knocking it, just noting the facts), which can be caused by yellow jelly beans, amongst other things; so, how could anyone miss the relevance ?

#10

For the record, I am not implying that you are in anyway silly. You could have easily understood the article. For eveyone else: I am not usually such a bitch - I think it’s quenched androgen receptor signal.

#11

does accutane users also have overexpressed androgen receptors in penile tissue ?

#12

And another question… we all waiting for Baylors to get released, but are there any new isotretinoin studies being conducted ? Maybe someone knows anything about new studies ?

#13

Presumably, since we often have the genital numbness and other genital signs/symptoms associated with PFS, yes. No studies have directly shown this in post-Isotretinoin patients though.

.

Unfortunately, no. Not even anything in the works at this stage.

#14

Are you aware of whether or not this FOX01 has been looked at by anyone doing any of the PFS studies? Have you seen it discussed by anyone anywhere outside of within that one article?

#15

I expect they will have in the coming study as FOXO1 is repressive of the AR via binding to its N terminal domain, which regulates AR transcriptional activity(1).

(1) FoxO1 Mediates PTEN Suppression of Androgen Receptor N- and C-Terminal Interactions and Coactivator Recruitment

3 Likes
#16

this is FOXO1 in relation with AR

FOXO1 blocks AR activity via both direct and indirect mechanisms in PCa. FOXO1 can bind to AR and affect its transcriptional activity. FOXO1 can mediate the signaling that controls the activity of AR in PCa. However, FOXO3 upregulates AR expression via binding to the promoter of AR. Therefore, FOXO factors and AR serve as important links between metabolism, the PTEN/AKT pathway and nuclear receptor activation in PCa. Targeting the FOXA and FOXO factors with drugs may offer selective means of affecting AR activity in CRPC patients.

Latest Literature to support FoxO1 theory (foxo1 ,foxo3 upregulation)

#17

I am quite convinced about FOX01. I got also a problem with hair growth after accutane. It looks like telogen effluvium

Isotretinoin has been demonstrated to affect hair growth.237 In equine hair follicles in vitro isotretinoin modified sheath-shaft interaction.238 It has recently been shown that ATRA induces premature hair follicle regression and induced a catgen-like stage in human hair follicles.239 Hair shaft elongation declined significantly already after 2 days in the ATRA-treated group, and approximately 80% of the ATRA-treated hair follicles had prematurely entered catagen-like stage at day 6, compared with 30% in the control group. This corresponded to an upregulation of apoptotic and a down-regulation of Ki67-positive cells in ATRA-treated hair follicles,239 thus pointing again to the induction of apoptosis, the hallmark of FoxO signaling.

Can we explain isotretinoin’s adverse effects on hair growth by FoxO-driven apoptosis and induction of catagen? A reasonable explanation would be that isotretinoin-induced FoxO impairs β-catenin signaling which is most important for hair growth. In fact, is has been shown that upregulated nuclear FoxOs binds nuclear β-catenin and divert β-catenin signalling from Tcf/Lef1 interaction ([ Fig. 5 ](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219165/figure/F5/)).135 Thus, upregualted FoxOs by isotretinoin would explain impaired β-catenin signaling leading to apoptosis and reduced growth and differentiation of hair follicles, explaining isotretinoin-induced FoxO-mediated hair loss.