Propecia DOES NOT inhibit neurosteroids!

[ajax]

so do you think allapregnolone supplementation could help?

[ajax]

so do you think allapregnolone supplementation could help?

[tim1911]

Allopregnanolone, a neuroactive steroid mainly secreted by adrenals and gonads

ncbi.nlm.nih.gov/pubmed/20530984

[tim1911]

We studied the tissue distribution and cellular localization of 5 alpha-reductase 2, the human prostatic isoenzyme, in different human tissues, both cryostat-sectioned and paraffin-embedded. Polyclonal antibodies raised in rabbits against a native peptide (C-terminal amino acids 229-254) or synthetic peptides (amino acids 234-245), either as carrier-conjugated linear peptides or multiple antigen peptides (MAP), were assayed for specificity and sensitivity with Western blotting and an ELISA system. One antibody showing monospecificity on Western blots and in ELISA was used for immunohistochemical detection of the respective antigen in tissues from male and female subjects. Positive cells were found (with decreasing intensity) in inner epithelial sheath of hair follicles, pyramidal cells of the cerebral cortex, hepatocytes and bile duct cells, prostate epithelial cells, seminal vesicle epithelial cells, endothelial cells of small vessels, fat cells, fibrocytes of genital and extragenital organs, and smooth muscle cells of prostate and seminal vesicles. Some variation in the immunoreactivity of testis and ovary tissue was seen with different antibodies. 5 alpha-Reductase 2 is obviously not restricted to androgen target organs in the male, but is present in a large number of cells and tissues in both males and females.

ncbi.nlm.nih.gov/pubmed/8157936

[BP7667]

Well that article pretty much hits on every place in my body that’s fucked up.

[tim1911]

To contrast the previously described distribution of 5 alpha-reductase isoenzyme 2 in human organs we have raised synthetic C-terminal peptides of human 5 alpha-reductase isoenzyme 1 (h 5 alpha r1) and isoenzyme 2 (h 5 alpha r2) respectively, and studied the cellular and subcellular distribution of both isoforms of this key enzyme of testosterone metabolism using the human prostate gland as a reference. h 5 alpha r1, which in Western blots of human prostatic proteins had an apparent molecular weight of 23 kDa, was localized immunohistochemically in the nucleus of prostatic epithelial and stromal cells. Ultrastructurally, it was closely associated with the nuclear matrix. The apparent molecular weight of h 5 alpha r2 was 26 kDa in Western blotting of human prostatic proteins. In immunohistochemically processed sections, it was seen in the cytoplasm of prostatic epithelial as well as stromal cells. An organ screening with genital and extragenital tissues of males and females was performed and to elucidate the distribution of the isoenzymes. Presence of both isoenzymes was demonstrated for a number of tissues, including the central nervous system, the urogenital tract, the respiratory tract, the gastrointestinal tract, skin, and the endocrine system. The divergent localization of 5 alpha-reductase isoenzymes points to potentially different functions in various organs. In view of the nuclear localization of isoenzyme 1, its close spatial relationship with the androgen receptor is presumed to indicate a close association with the receptor mechanism.

ncbi.nlm.nih.gov/pubmed/9078395

[Oscar]

If that study by AUMÜLLER is accurate it would really help explain things (pyramidal cells in the amygdala etc), although it seems to contradict all the other studies posted.

hindawi.com/journals/au/2012/530121/

Numerous reports exist in the literature on the expression pattern of 5α-R1 and 5α-R2 in human
tissue at various stages of development. The results vary due to differences in antibody sensitivity and specificity,
mRNA analysis (in situ hybridization versus northern blotting versus reverse transcriptase-polymerase chain reaction),
protein analysis (immunohistochemistry versus western blotting), tissue preparation, nature of tissue, evaluation of results,
tissue fixation protocols, and control tissue. In addition, normal, benign, and malignant human tissue specimens are heterogeneous
with variable expression of proteins among specimens from different individuals and within the same specimen, that is, inter- and intraindividual variability.
Therefore, a summary of many studies that discussed the tissue distribution of 5α-R1-3 in different human tissues was tabulated to demonstrate differences in results (Table 3).

[tim1911]

Oscar im going have to go against you on this one mate, i think finasteride does inhibit neurosteroids,

Finasteride is the 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostate hyperplasia and androgenetic alopecia. The 5alpha-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone, steroids modulating the action of gamma-aminobutyric acid on GABA receptors. These neuroactive steroids possess anticonvulsant, antidepressant and anxiolytic effects. The objective of the study was to determine the effect of finasteride therapy on a broad steroid spectrum in men with benign prostate hyperplasia. A group of 20 men with benign prostate hyperplasia was involved in the present study. Finasteride in the daily dose of 5 mg/day was administrated for 4 months. In all individuals, their hormonal profile of steroid hormones was determined before and after 4 months lasting finasteride treatment. Finasteride treatment resulted in a significant decrease all alpha-reduced and increase of most 5beta-reduced metabolites of testosterone and progesterone as well as in an increase of 7alpha-hydoxyderivatives, which are known as neuroactive steroids acting by modulation of GABAA and NMAD receptors in the brain. In the course of finasteride treatment the decrease of the concentration of circulating steroids with known inhibitory activity on GABA-ergic excitation in the brain is very probably an important factors contributing to the development of the symptoms of depression seen in some isolated cases of finasteride administration.

ncbi.nlm.nih.gov/pubmed/19655698

pmr.cuni.cz/Data/Files/PragueMed … 9a0025.pdf

Last link is the study with this table viewtopic.php?f=24&t=6094&hilit=well

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Heres the situation for me,

While on Finasteride 5a reduced steroids are inhibited, with light to mild side effects.

Finasteride is quit, side effects resolve, steroid metabolism returns to normal? (Unanswered question)
Neurosteroids return to normal?(Unanswered question)

The “crash happens” which leaves the “user” with a neurosteroid profile that resembles someone taking finasteride, but with side effects that range from mild to heavy.

So for me this is enough evidence to say that low levels of 5a reduced metabolites is not enough to be causing all these side effects. Otherwise people on Finasteride would be lining up at hospitals.

What ever is preventing the 5ar2 metabolising these steroids is what is causing our problems (something replicating the action of finasteride), and the fact that many have come back to normal before crashing has to be a clue, what the clue is …

[Oscar]

^That study is the first one posted in this thread. It only discusses neuroactive steroids in plasma, not CSF, therefore it doesnt describe what goes on in the CNS.

The only study that says 5aR2 is in the brain is that 1994/1996 study by Aumüller et al. But many other studies say something different.

I agree that if 5ar2 was in the brain it would really help (viewtopic.php?f=27&t=7668) But If Aumüller’s studies where the only saying there wasnt 5aR2 in the brain they wouldnt be given much weight.

[tim1911]

A couple of points, he has found it not only to be in the brain but with a higher intensity than the prostate.

Positive cells were found (with decreasing intensity) in inner epithelial sheath of hair follicles, pyramidal cells of the cerebral cortex, hepatocytes and bile duct cells, prostate epithelial cells, seminal vesicle epithelial cells, endothelial cells of small vessels, fat cells, fibrocytes of genital and extragenital organs, and smooth muscle cells of prostate and seminal vesicles.

And he has found it in the CNS in hi 1996 study, like you i find it hard who to believe, but if it is true it goes along way to solving this condition.

[tim1911]

1 of 2 things could be happening

1. There is 5AR2 in the brain/CNS as the above paper suggests,

2. The low neurosteroids in the CSF are due to low levels being metabolised at peripheral sources, gonads, adrenals.
   I have read in a few papers that neurosteroids produced in other parts of the body accumulate in the brain.

An established fact is Propecia does inhibit neurosteroids in the blood. I can find no information about the CSF being tested while someone is on Propecia, which is surprising.

But i will say it again, low levels of neurosteroids is not enough to do this to us otherwise we would have been like this on Finasteride.

For me it stinks as an enzyme problem and im struggling to find how the receptor is involved.

[Oscar]

casereports.bmj.com/content/2013 … 4.abstract

Temporal lobe epilepsy exacerbation during pharmacological inhibition of endogenous neurosteroid synthesis

We report the case of a woman who presented cryptogenic temporal lobe seizures from the age of 43 years. Antiepileptic drug (AED) treatment with carbamazepine was able to control seizures for 1 year, but seizures relapsed and an add-on treatment with lamotrigine was started without achieving seizures control. The patient’s medical history was unremarkable except for a mild hirsutism for which she was taking finasteride since 45 years of age. In view of the possible relationship between finasteride, a known inhibitor of neurosteroids synthesis, and patient’s seizures exacerbation, we stopped finasteride resulting in prompt recovery of seizures control. It is know that 5α-dihydrosteroids are precursors of powerful positive modulators of γ-aminobutyric acid-A inhibitory currents and exert antiseizure effects in animal epilepsy models. This case supports the hypothesis that endogenous neurosteroids can modulate seizure susceptibility and response to AEDs also in humans, suggesting their possible use as a new therapeutic option.

[tim1911]

Physical evidence that finasteride inhibits neurosteroids in the brain? Do you think this backs up Aumüller, that there is 5ar2 in the cerebral cortex?