5-ar and Neurosteroid Synthesis: 2 Studies

[Dubya_B]

Just a couple noteworthy articles on 5-ar and neurosteroids:

R. C. Agis-Balboa, A. Guidotti, and G. Pinna, “5α-reductase type I expression is downregulated in the prefrontal cortex/Brodmann’s area 9 (BA9) of depressed patients,” Psychopharmacology, vol. 231, no. 17, pp. 3569–3580, Sep. 2014.

http://link.springer.com/article/10.1007/s00213-014-3567-5

We thus hypothesized that decreased CSF levels of Allo in depressed patients could reflect a brain dysfunction of 5α-RI…
…Although in a small number of patients, this finding is in-line with previous reports in the field that have observed an increase of Allo levels in CSF and plasma of depressed patients following antidepressant treatment. Hence, the molecular mechanisms underlying major depression may include a GABAergic neurotransmission deficit caused by a brain Allo biosynthesis downregulation, which can be normalized by SBSSs.

It’s a shame the “SBSSs” they used are associated with sexual dysfunction. (SSRIs)

J. M. Torres and E. Ortega, “Differential regulation of steroid 5α-reductase isozymes expression by androgens in the adult rat brain,” FASEB J, vol. 17, no. 11, pp. 1428–1433, Aug. 2003.

http://www.fasebj.org/content/17/11/1428

The enzyme 5α-reductase (5α-R) is present in many mammalian tissues, including the brain. The physiological importance of 5α-R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5α-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the γ-aminobutyric acid receptor (GABAA-R). 5α-R occurs as two isoforms, 5α-R type 1 (5α-R1) and 5α-R type 2 (5α-R2). We studied the effects of T and DHT on the mRNA levels of both 5α-R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one-step quantitative RT-PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5α-R are expressed in the cerebral cortex of adult rats. The gene expression of 5α-R type 2 is under the positive control of T and DHT. The gene that codes for 5α-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5α-R isozymes in the physiology of the central nervous system

[bens]

The 2nd study is very interesting. But I’ve read conflicting information that suggests the opposite.

[Finatruth]

Ah look at what the genius Finatruth wrote two years ago!

viewtopic.php?f=24&t=8550&p=76706&hilit=Prefrontal+cortex+metabolism#p76706

viewtopic.php?f=27&t=8399&p=75275&hilit=Prefrontal+cortex+metabolism#p75275

I’m telling everyone two years ago where the problem lies, even telling you that I’m so right you can’t print it!! We are getting closer to solving this mystery!

Where are you luckfax?

[dgreene]

I hope to God the scientists think of a combination of medications that can reverse this soon. That study saying 5 ar type 1 is negatively regulated by T and DHT is very interesting. That could explain the DHT surge and then crash.

[Finatruth]

I really think, and that’s where all this is heading including Traish’s recent journal article, is to combat the metabolic dysfunction best we can, absolute exercise and absolute clean diet, and of course 7-10 or more years

[bens]

Unfortunately it doesn’t explain sides experienced on the drug. I am curious about all of this enzyme regulation stuff though. Not just 5ar, but the 3aHSD enzymes as well.

[Dubya_B]

I think these studies only describe one aspect of the problem.

Some others on this board have mentioned that proper androgen receptor signalling might be essential for stimulating both 5-ar metabolism and 3a-HSD metabolism.