GABA and the HPTA

General Discussion
#1

On this board, we’ve spoken much about different mechanisms of action by which finasteride may effect human physiology. Two, in particular, are:

  1. Brain effects of a blockade of Progesterone metabolism, notably 5á-THDOC and 3á,5á-THP.

“5á-THDOC and 3á,5á-THP are the most potent positive modulators of GABAA” (ncbi.nlm.nih.gov/sites/entre … t=Abstract)

…Noting also that inhibition of DHT (in our “other” metabolic system) will in turn lower androstanediol, with which it undergoes reversible reaction. Androstanediol, too, is a positive modulator of GABA.

  1. HPTA effects of a blockade of T -> DHT conversion. In particular, increasing T and E, thus suppressing GnRH release.

But both of these systems are, in fact, highly connected

endo.endojournals.org/cgi/conten … 005-0788v1

“Our results indicate GABAergic inputs help generate a portion of action potentials in GnRH neurons; this fraction depends on the level of GABA transmission and postsynaptic responsiveness. The complexities of GnRH neuron response to GABA make this a potentially critical integration point for central regulation of fertility.”

So the message here may be this: take all the clomid, tamoxifern, TRT, DIM you want, you’ll still be treating the symtom but not the cause, which is rooted in GABA regulation of the HPTA.

I take John Doe’s recovery article in the recovery section as evidence that this may be the case (I know, one piece anecdotal evidence from the internet, right?). Both his mental and physical sides cleared up all at once, implying a common cause for both. Perhaps GABA regulation returned to normal, which in turn returned GnRH levels to normal, which acted to restore the HPTA.

Just speculating…

#2

Interesting… but what about the anxiety that many experience while on Fin due to depleted Allopregnanolone/GABAA, and the fact it resolves after discontinuing – indicating levels of Allo/GABAA go back to normal within a short time frame, yet other side effects still persist? For example, I had anxiety while on the drug that went away within a few months of quitting but still am not “horny” in my head, for one.

As you know, GABAA acts as a calming/inhibitory neurotransmitter, which can be significantly downregulated via Fin’s blockade of Progesterone --> Allopregnanolone conversion (Allo works on GABAA)… perhaps in some people these levels take a long time to recover, despite the abolishment of anxiety after quitting?

One can easily purchase GABAA supplements in any store, and see if they make any difference. I suspect for those of us without the anxiety there may be other issues still at play, but I suppose it wouldn’t hurt to try… probably make you more tired/drowsy though.

#3

GABA also appears to regulate GnRH receptor transcription…

endo.endojournals.org/cgi/conten … 587?ck=nck

“This experiment demonstrates for the first time that GABAergic neurotransmission, through GABA-A receptors, is involved in the regulation of GnRHR transcript level in the rat hypothalamus.”

#4

Right, and corroborating that might be this article I posted some time back showing how lowered allopregnenolone levels in alcoholics did in fact return to normal: ncbi.nlm.nih.gov/sites/entre … t=Abstract
“…ALLO and THDOC plasma levels did not differ from those of control subjects during the late withdrawal phase when anxiety and depression scores were low.”

But who really knows…maybe allo and other positive modulators of GABAA returned to normal levels in some parts of the brain, but not the hypothalamus, where it functions to enhance production of GnRH and GnRH receptors? Maybe (perhaps uniquely for us fin-users) positive modulators of GABAA did not return completely to normal levels so that we have enough to not feel anxiety (or perceive anxiety), yet still are not mustering enough GABAnergic stimulation to release adequate quantities of GnRH and its receptor.

Right, except it wouldn’t be GABA per se that needed to be address, but instead positive modulators of GABA, like allopregnenolone.

I might also reference the examples of recoveries on this site involving therapies targeting neurotransmitters levels, namely progesterone and dopamine.

If you recall letsconvience, who saturated his brain with dopamine (using both precursors and reuptake inhibitors - which I think is insane), found that he regained sexual function. If we can find evidence that dopamine either increases GABA expression or expression of a positive modulator of the GABAA receptor, then it might be evidence in favor of the mechanism I described.

Also, most obviously, are the progesterone people. Increase progesterone has in fact been shown empirically to increase allo (mentioned in: blackwell-synergy.com/doi/pd … 06.00053.x).
The theory is different, but results are the same: “I cannot express enough how I have seen people recover fully from very severe propecia problems through following Dr. Wilson’s adrenal fatigue book and through using 5 mg per day of progesterone cream. The results are amazing.”

On the whole though, I’m wary of both of these treatments, as they rely on ‘replacement’ methods, which I would be afraid were acting to decrease my endogenous production.

#5

Based on this theory, I have to say that cranial electrostimulation looks promising.

This therapy involved small shocks to the brain, and is known to have a number of wide-ranging positive effects. These results are for the most part unsubstantiated, but a harvard metastudy did confirm positive effects on anxiety ( ncbi.nlm.nih.gov/sites/entre … t=Abstract ).

Most interestingly, electrical engineers studying CES have found that the result of CES treatment is to stimulate the “thalamic region” with tiny amounts of electric charge. ( elixa.com/estim/CES.htm )

.,it also appears to boost GABA, according to this site

And from wikipedia ( en.wikipedia.org/wiki/Cranial_el … timulation ):
“During CES, an electric current is focused upon the hypothalamic region”

No clear idea of what the mechanism could be, but it’s effects are known to be corrective in the long-term, it’s not a ‘replacement therapy’, and it acts on that one area of special interest, the hypothalamus.

Might be worth looking into further…

#6

“Electrical stimulation of the hypothalamic and limbic pathways in experimental animals results in erection, although a review of reports
of brain stimulation in awake man during stereotaxic neurosurgery concluded there had been no reliable instances of erection. However,
damage to the dorsolateral hypothalamic nuclei during stereotaxic surgery for the relief of myoclonus, may cause loss of libido and
erectile dysfunction, whereas hypersexuality occurs as a consequence of septal injury.”

wfneurology.org/docs/pdf/Munsat_chapter9.pdf

#7

content.karger.com/ProdukteDB/pr … elNr=70897

“While the physiological significance of this peripheral neuroendocrine system conserved throughout species remains to be elucidated, its mere presence in humans suggests the possibility that clinically used drugs might be able to interfere with testicular function.”

So to my knowledge, at this point, GABA is essential for proper HPTA function in 3 ways:

  1. Enhances GnRH release in hypothalamus
  2. Signals GnRH receptor synthesis
  3. Is involved in some unknown mechanism in the testes themselves.

Note that presumably, 5AR type 2 would convert progesterone to allopregnenolone in the testes without the partial inhibition of brain 5AR type 1.

#8

Well this is interesting:

pomology.org/003/555/003555228.html

“In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor. We speculate that the inhibitory effect of allopregnanolone on the HPG axis may also be caused by its ability to suppress hypothalamic GnRH release.”

Obviously, this is the opposite of what I had been thinking…that GABA acted to enhance GnRH tone. In fact, I had misinterpreted the above articles. In the article about GABA effect on GnRH receptor transcription, they found:

“The activation of GABA-A receptors with muscimol resulted in a significant inhibition in GnRHR transcript level in both the pMBH and POA but not in the pituitary.”

The first article I mention, “Endogenous GABA can excite GnRH neurons,” says nothing more than that. Whether the GABA causes GnRH release in those neurons was not studied. Only the fact that GABA “has an effect” was determined.

So, my conclusion from all this has basically been reversed: In fact, allopreganalone, presumably through its positive modulation of the GABAA receptor, suppresses GnRH release, and hence the HTPA.

I suppose this means, for fin-users, that if any effect of fin on the HTPA though its action on neurosteroids is to be expected, it should be one that actually enhances the HTPA.

That’s weird.

#9

I m thinking at this theory too from some days…about gaba it s related the fact that many ppl has emotional problems too, another proof is that paul and ithappens recovered by using ghb.

#10

I’ve never been able to find what supplements are specifically reccommended by Dr Wilson. Is there a list or a link anywhere? Interested in this treatment direction as well.

#11

Know this is a very old thread, but galapagos mentioned a CES device to stimulate neurotransmitters - they now seem to be available online for under 1000 dollars.

fisherwallace.com/

#12

Golf,

Thanks for that link. I’m most likely going to purchase this. I’ve used frequency machines in the past with very good results. (Rife)

I’ll keep everyone posted.

#13

No prob. There are more out there - such as this one:

bio-medical.com/product_info … 5QodZDw0GA

Let me know how it goes.