Thyroid Hormones and AR Gene Expression

[mariobros]

This is not actually a theory in it’s own, more a possible piece of the puzzle. I believe there may be a link between androgen receptor gene expression and thyroid function. Thyroid hormones appear to modulate nerve growth factor, and nerve growth factor modulates androgen receptor expression.

Nerve growth factor induces the re-expression of functional androgen receptors and p75NGFR in the androgen-insensitive prostate cancer cell line DU145

DU145 cells were treated with NGF, then ARs and NGF receptor p75NGFR expression and
telomerase activity were studied. Finally, we investigated whether re-expression of ARs could restore
the androgen sensitivity in this cell line…NGF treatment induced a reversion of DU145 cells to a less malignant
phenotype, characterized by the re-expression of ARs and p75NGFR NGF receptors. Re-expression of ARs restored the androgen sensitivity, as suggested by the fact that exposure to dihydrotestosterone stimulated the growth of NGF-treated DU145 cells.

eje-online.org/cgi/reprint/147/3/407.pdf

Thyroid hormones precociously increase nerve growth factor gene expression in the submandibular gland of neonatal mice

T4 increased NGF mRNA levels by 100-fold in both male and female immature mice…Determination of the effect of thyroid hormone treatment on SMG NGF gene expression by nuclear run-on assay demonstrated a significant transcriptional effect of T4…The results show that thyroid hormones increase NGF gene expression in the SMG of the immature male and female mouse. This effect is due in part to a significantly enhanced rate of gene transcription.

Glucocorticoids differentially increase nerve growth factor and basic fibroblast growth factor expression in the rat brain

Adrenocorticotropin hormone (ACTH) and adrenal steroids may influence trophic processes operative in neuronal plasticity. Because nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) participate in neuronal trophism, we have investigated whether adrenal steroids induce the expression of these two trophic factors in the rat brain…Our data suggest that NGF and bFGF represent a link by which the adrenal cortical system can exert trophic action on the CNS.

jneurosci.org/cgi/content/short/16/6/2141

Here is a more direct link:

Thyroid hormone effects on androgen receptor messenger RNA expression in rat Sertoli and peritubular cells.

These results indicate that T3 is an important regulator of the postnatal Sertoli cell AR mRNA increase. The additive effects of maximally stimulatory doses of FSH and T3 suggest these hormones work through different mechanisms to increase AR mRNA. TR mRNA expression in peritubular cells indicates these cells may be direct T3 targets, though the function of T3 in these cells is unknown.

ncbi.nlm.nih.gov/pubmed/9496232

The following study also demonstrates that Acetyl L-Carnitine is able to increase NGF levels.

Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats.

The stimulation of NGF levels in the CNS can be attained when ALCAR is given either for long or short periods to senescent animals of various ages, thus indicating a direct effect of the substance on the NGF system which is independent of the actual degenerative stage of the neurons. Furthermore, long-term treatment with ALCAR completely prevents the loss of choline acetyltransferase (ChAT) activity in the CNS of aged rats, suggesting that ALCAR may rescue cholinergic pathways from age-associated degeneration due to lack of retrogradely transported NGF.

[Oscar]

Wow! This study is a great find! eje-online.org/cgi/reprint/147/3/407.pdf

Data presented here suggest that NGF treatment
induces a reversion of the androgen-independent/ARnegative
prostate cancer cell line DU145 (22, 23) to
a less malignant, more differentiated phenotype
with low telomerase activity, characterized by the
re-expression of ARs and p75NGFR. It should be emphasized
that ARs restore the androgen sensitivity, as
suggested by the fact that exposure of NGF-treated
DU145 cells to the androgen hormone dihydrotestosterone
(DHT) stimulated cell growth, and that this
effect was blocked by the anti-androgen drugs,
hydroxyflutamide (HF) and cyproterone acetate (CPA)
…
The relevance of the re-expression of functionally
active ARs is underlined by the part played by ARs in
the prostate. Mechanisms by which prostate cancer
cells escape androgen ablation and become independent
of the need for androgens are not yet well understood.
It has been proposed that development of the
androgen independency can occur by a variety of
mechanisms, such as environmental adaptation, multifocal
origin or genetic instability (26). The vast
majority of androgen-independent prostate tumors
express ARs highly; many paradigms, indeed, relate
the finding of AR overexpression to the development
of hormone resistance, and it has been suggested that
amplifications or mutations, or both, of ARs may play
a part in altering sensitivity to androgens (27).
However, 20–30% of advanced metastatic hormoneindependent
prostate cancer is characterized by a
significant loss of AR expression, as a result of
transcriptional silencing that does not comprise
either deletion or mutational mechanisms (27).
Both in clinical tumors and in prostate cancer cell
lines, the transcriptional silencing of ARs involves
hypermethylation of the AR promoter and histone
deacetylation, known as epigenetic mechanisms (28).
Results reported here lead to the hypothesis that
NGF treatment could modulate gene expression in
the DU145 prostate cancer cell line through the epigenetic
regulation of transcription. This suggestion is
supported by the finding that this phenomenon also
occurs in PC12 cells, in which NGF-mediated differentiation
induces downregulation of the enzyme
catalyzing the DNA methylation reaction, namely
DNA methyltransferase (29). Furthermore, the inhibition
of this enzyme restores androgen sensitivity in
DU145 cells, and it has been proposed that this effect
could be due to a partial demethylation of the AR
(30).

So nerve growth factor is possibly the cure?
en.wikipedia.org/wiki/Nerve_growth_factor
…And it has the side effect of increased longevity and mental capacity (see this old crone, en.wikipedia.org/wiki/Rita_Levi-Montalcini who discovered the stuff and has been using it daily)

But nothing to do with the thyroid imo.

[mariobros]

It’s possible, the question is how to administer it and at what dose because the study posted was in vitro. I imagine it will need to be a fairly significant amount. The good news is that it may be more specific and significantly less toxic than other demethylating agents.

I posted the link to thyroid hormone’s modulating NGF just because i thought someone might have an opinion on it but i didn’t want people to start talking about thyroid hormone on the AR gene hypermethylation thread.

I will post a link to the original study in that thread.

[191]

good work!

I think this is interesting. I believe there is a study showing thyroxine upregulates androgen receptors and it could be via this process. Personally i noticed positive effects of T3 treatment at first e.g. strong erections until i became hyperthyroid. Thyroxine or T3 ups your SHBG too so sweeps up more free testosterone.

Problem with acetyl l-cartinine is i’m not sure its very effective in humans.

Dr Jay Goldstein(who seems to really know his drugs) says:

Acetyl-L-Carnitine: In theory, a good drug. It should work as an acetyl group donor to increase acetylcholine, and the camitine has already been shown to be effective in a double-blind experiment by the Drs. Plioplys. Acetyl-L-camitine also increases the levels of nerve growth factor (which are four times normal in the spinal fluid of FMS patients) and increases other transmitters like adenosine and ATP. In practice, a semi-dud.

sunshine35446.yuku.com/topic/2068/t/Dr-Jay-Goldstein-39-s-Protocol.html

I believe treating the thyroid is not the solution as the body will try to maintain its homeostasis and will only mess our systems up further.

Its an interesting find though and could explain why some people find benefit in it. The question of “depth” as i mention in the methylation post I would hypothese plays a part in how one reacts.