5α-Reductase / PFS connections Research

[Ghost]

I'm simply just throwing out studies in case they are of interest to anyone. I found one of the very few things that has been shown to increase 5α-Reductase activity. Interesting also becuase it is co-authored by our friend Dr. Melcangi from the University of Milan.

Activation of the Liver X Receptor Increases Neuroactive Steroid Levels and Protects from Diabetes-Induced Peripheral Neuropathy
Gaia Cermenati, Silvia Giatti, Guido Cavaletti, Roberto Bianchi, Omar Maschi, Marzia Pesaresi, Federico Abbiati, Alessandro Volonterio, Enrique Saez, Donatella Caruso, Roberto Cosimo Melcangi and Nico Mitro

"LXR ligand treatment of streptozotocin-treated rats increases expression in the sciatic nerve of steroidogenic acute regulatory protein (a molecule involved in the transfer of cholesterol into mitochondria), of the enzyme P450scc (responsible for conversion of cholesterol into pregnenolone), of 5α-reductase (an enzyme involved in the generation of neuroactive steroids)"

http://www.jneurosci.org/content/30/36/11896.short

[Bigmum]

I ' ve never seen it before...

[Ghost]

Cross-talk between the Androgen Receptor and the Liver X Receptor IMPLICATIONS FOR CHOLESTEROL HOMEOSTASIS

http://www.jbc.org/content/286/23/20637.full.html

[Dubya_B]

Thanks for posting that Ghost!

I have a few collections of similarly related studies.

NEUROSTEROIDS: Miscellaneous information concerning neurosteroid synthesis and physiological/psychological effects. DHT, T, estrogens, progestins, and DHEA as neurosteroids are included.

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

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/10.100 ... 014-3567-5

R. C. Melcangi and G. C. Panzica, “Allopregnanolone: State of the art,” Progress in Neurobiology, vol. 113, pp. 1–5, Feb. 2014.
http://www.sciencedirect.com/science/ar ... 8213000981

S. R. King, “Emerging Roles for Neurosteroids in Sexual Behavior and Function,” Journal of Andrology, vol. 29, no. 5, pp. 524–533, Sep. 2008.
http://onlinelibrary.wiley.com/doi/10.2 ... 0/abstract

S. R. King and D. M. Stocco, “Steroidogenic Acute Regulatory Protein Expression in the Central Nervous System,” Frontiers in Endocrinology, vol. 2, 2011.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355896/

S. R. King et al., “An Essential Component in Steroid Synthesis, the Steroidogenic Acute Regulatory Protein, Is Expressed in Discrete Regions of the Brain,” J. Neurosci., vol. 22, no. 24, pp. 10613–10620, Dec. 2002.
http://www.jneurosci.org/content/22/24/10613

D. S. Reddy, “Neurosteroids: Endogenous Role in the Human Brian and Therapeutic Potentials,” Progress in brain research, vol. 186, p. 113, 2010.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029/

C. Escudero et al., “Allopregnanolone prevents memory impairment: effect on mRNA expression and enzymatic activity of hippocampal 3-α hydroxysteroid oxide-reductase,” Brain Res. Bull., vol. 87, no. 2–3, pp. 280–285, Feb. 2012.
https://www.researchgate.net/profile/Fe ... uctase.pdf

R. Araki, S. Nishida, Y. Hiraki, K. Matsumoto, and T. Yabe, “DNA methylation of the GC box in the promoter region mediates isolation rearing-induced suppression of srd5a1 transcription in the prefrontal cortex", Neuroscience Letters, vol. 606, pp. 135–139, Oct. 2015.
http://www.sciencedirect.com/science/ar ... 4015301014

K. L. Edinger and C. A. Frye, “Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats,” Hormones and Behavior, vol. 50, no. 2, pp. 216–222, Aug. 2006.
http://www.sciencedirect.com/science/ar ... 6X06000559

K. S. L. Dalpatadu, “Role of neurosteroid (allopregnanolone) in the modulation of kisspeptin-gonadotropin releasing hormone pathway and mood disorders,” thesis, Monash University. Sunway Campus. Faculty of Medicine, Nursing and Health Sciences. Brain Research Institute, Jeffrey Cheah School of Medicine and Health Sciences, 2011.
http://arrow.monash.edu.au/vital/access ... nash:81855

N. Carrier and M. Kabbaj, “ERK2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone,” Biological Psychiatry, vol. 71, no. 7, p. 642, Apr. 2012.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307821/

L. Fester and G. M. Rune, “Sexual neurosteroids and synaptic plasticity in the hippocampus,” Brain Research, vol. 1621, pp. 162–169, Sep. 2015.
https://www.ncbi.nlm.nih.gov/pubmed/25452021

R. B. Dor, C. E. Marx, L. J. Shampine, D. R. Rubinow, and P. J. Sidt, “DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action,”chm Psychopharmacology, vol. 232, no. 18, pp. 3375–3383, Sep. 2015.
https://link.springer.com/article/10.10 ... 015-3991-1

K. Tsutsui and S. Haraguchi, “Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 2. Discovery of neurosteroids and pineal neurosteroids,” General and Comparative Endocrinology, vol. 205, pp. 11–22, Sep. 2014.
https://www.researchgate.net/profile/Sh ... eroids.pdf[/url]


NEUROSTEROIDS AND SEROTONERGIC CELLS:

V. Kaura, C. D. Ingram, S. E. Gartside, A. H. Young, and S. J. Judge, “The progesterone metabolite allopregnanolone potentiates GABAA receptor-mediated inhibition of 5-HT neuronal activity,” European Neuropsychopharmacology, vol. 17, no. 2, pp. 108–115, Jan. 2007.
http://www.sciencedirect.com/science/ar ... 7X06000332

M. Hajós, S. E. Gartside, and T. Sharp, “Inhibition of median and dorsal raphe neurones following administration of the selective serotonin reuptake inhibitor paroxetine,” Naunyn-Schmiedeberg’s Arch Pharmacol, vol. 351, no. 6, pp. 624–629.
http://link.springer.com/article/10.1007/BF00170162

G. S. Kranz et al., “High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People,” Biol. Psychiatry, vol. 78, no. 8, pp. 525–533, Oct. 2015.
http://www.ncbi.nlm.nih.gov/pubmed/25497691

C. L. Bethea, K. Coleman, K. Phu, A. P. Reddy, and A. Phu, “Relationships between androgens, serotonin gene expression and innervation in male macaques,” Neuroscience, vol. 274, pp. 341–356, Aug. 2014.
http://www.sciencedirect.com/science/ar ... 2214004643

O. Kc, T. S, B. Sj, and L. Ma, “13-cis-Retinoic acid alters intracellular serotonin, increases 5-HT1A receptor, and serotonin reuptake transporter levels in vitro.,” Exp Biol Med (Maywood), vol. 232, no. 9, pp. 1195–1203, Oct. 2007.
http://europepmc.org/abstract/MED/17895527

T. Pejchal, M. A. Foley, B. E. Kosofsky, and C. Waeber, “Chronic fluoxetine treatment selectively uncouples raphe 5‐HT1A receptors as measured by [35S]‐GTPγS autoradiography,” British Journal of Pharmacology, vol. 135, no. 5, pp. 1115–1122, Mar. 2002.
http://onlinelibrary.wiley.com/doi/10.1 ... 5/abstract

K. C. O’Reilly, J. Shumake, S. J. Bailey, F. Gonzalez-Lima, and M. A. Lane, “Chronic 13-cis-retinoic acid administration disrupts network interactions between the raphe nuclei and the hippocampal system in young adult mice,” European Journal of Pharmacology, vol. 605, no. 1–3, pp. 68–77, Mar. 2009.
http://www.sciencedirect.com/science/ar ... 9909000156

M. Robichaud and G. Debonnel, “Allopregnanolone and ganaxolone increase the firing activity of dorsal raphe nucleus serotonergic neurons in female rats,” The International Journal of Neuropsychopharmacology, vol. 9, no. 02, pp. 191–200, Apr. 2006.
http://journals.cambridge.org/abstract_ ... 570500595X

M. Robichaud and G. Debonnel, “Oestrogen and Testosterone Modulate the Firing Activity of Dorsal Raphe Nucleus Serotonergic Neurones in Both Male and Female Rats,” Journal of Neuroendocrinology, vol. 17, no. 3, pp. 179–185, 2005.
http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

M. Robichaud and G. Debonnel, “Modulation of the firing activity of female dorsal raphe nucleus serotonergic neurons by neuroactive steroids,” J Endocrinol, vol. 182, no. 1, pp. 11–21, Jul. 2004.
http://joe.endocrinology-journals.org/content/182/1/11

R. Klink, M. Robichaud, and G. Debonnel, “Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part II. Regulatory mechanisms,” Neuropharmacology, vol. 43, no. 7, pp. 1129–1138, Dec. 2002.
http://www.sciencedirect.com/science/ar ... 0802002186

R. Klink, M. Robichaud, and G. Debonnel, “Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part I: Effects of gender and pregnancy,” Neuropharmacology, vol. 43, no. 7, pp. 1119–1128, Dec. 2002.
http://www.sciencedirect.com/science/ar ... 0802002198


SSRI HORMONAL EFFECTS:

A. J. Devall, J. M. Santos, J. P. Fry, J. W. Honour, M. L. Brandão, and T. A. Lovick, “Elevation of brain allopregnanolone rather than 5-HT release by short term, low dose fluoxetine treatment prevents the estrous cycle-linked increase in stress sensitivity in female rats,” European Neuropsychopharmacology, vol. 25, no. 1, pp. 113–123, Jan. 2015.
http://www.sciencedirect.com/science/ar ... 7X14003289

J. P. Fry, K. Y. Li, A. J. Devall, S. Cockcroft, J. W. Honour, and T. A. Lovick, “Fluoxetine elevates allopregnanolone in female rat brain but inhibits a steroid microsomal dehydrogenase rather than activating an aldo‐keto reductase,” British Journal of Pharmacology, vol. 171, no. 24, pp. 5870–5880, Dec. 2014.
http://onlinelibrary.wiley.com/doi/10.1 ... 1/abstract

N. W. Jacobsen, C. H. Hansen, C. Nellemann, B. Styrishave, and B. Halling-Sørensen, “Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay,” Toxicol In Vitro, vol. 29, no. 7, pp. 1729–1735, Oct. 2015.
http://www.ncbi.nlm.nih.gov/pubmed/26162595

C. Tanrikut and P. N. Schlegel, “Antidepressant-associated changes in semen parameters,” Urology, vol. 69, no. 1, p. 185.e5-7, Jan. 2007.
http://www.ncbi.nlm.nih.gov/pubmed/17270655

P. Prasad, S. Ogawa, and I. S. Parhar, “Serotonin Reuptake Inhibitor Citalopram Inhibits GnRH Synthesis and Spermatogenesis in the Male Zebrafish,” Biol Reprod, vol. 93, no. 4, p. 102, Oct. 2015.
http://www.biolreprod.org/content/93/4/102

M. R. Safarinejad, “Evaluation of Endocrine Profile and Hypothalamic-Pituitary-Testis Axis in Selective Serotonin Reuptake Inhibitor-Induced Male Sexual Dysfunction:,” Journal of Clinical Psychopharmacology, vol. 28, no. 4, pp. 418–423, Aug. 2008.
http://www.ncbi.nlm.nih.gov/pubmed/18626269

V. Uzunova et al., “Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine,” Proc. Natl. Acad. Sci. U.S.A., vol. 95, no. 6, pp. 3239–3244, Mar. 1998.
http://www.ncbi.nlm.nih.gov/pubmed/9501247

G. Pinna, E. Costa, and A. Guidotti, “Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake,” Psychopharmacology, vol. 186, no. 3, pp. 362–372, Jun. 2006.
http://link.springer.com/article/10.100 ... 005-0213-2

L. D. Griffin and S. H. Mellon, “Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes,” PNAS, vol. 96, no. 23, pp. 13512–13517, Nov. 1999.
http://www.pnas.org/content/96/23/13512



It really does suck that there are so many missing links in the research. In particular, there is very little research regarding PFS/Finasteride and neurostransmitters, maybe with the exception of a few studies on dopaminergic system. It can be said with confidence that both SSRIs and Finasteride decrease DHT levels in the nervous system and perhaps DHP also. Accutane inhibits transcription of 5-ar and decreases DHT in skin, so it seems reasonable to assume it does the same in nervous system, leading to sexual dysfunction for some of us.

Didn't include the studies above, but Melcagni and others in neuroendocrinology have found similar, but milder, deficits of neurosteroids and 5-ar expression in Multiple Sclerosis patients and mouse models of MS as were found in PFS patients. It's worth noting that up to 60% of MS patients complain of some degree of sexual dysfunction, mainly loss of libido.

Will post some more studies here another day, if that is cool with you guys.

[Bigmum]

Wow it's huge amount of studies

[Ghost]

Damn. Welcome to the forum. Thanks so much.

[future-recovery]

What really differs from SSRIs:
Only 5% get sexual dysfunction during the treatment in contrast to 60 or 70% with SSRIs.
Moreover about 1% of men (16-42 years old) who take finasteride get persistent erectile dysfunction after the discontinuation. So possibly PFS could be extremely common. http://www.pfsfoundation.org/news/feinb ... hair-loss/

[Recovery]

Frye CA1, Rhodes ME.; Fluoxetine-induced decrements in sexual responses of female rats and hamsters are reversed by 3α,5α-THP
J Sex Med. 2010 Aug;7(8):2670-80

https://www.ncbi.nlm.nih.gov/pubmed/20412429

[Bigmum]

Pfs seems to be common condition
Look at this
https://www.ncbi.nlm.nih.gov/pubmed/24928450

[Juvo]

Another odd thing is the male prevalence. Ghost, do you know how the men/women ratio?