EXCLUSIVE : The What & The How of DHT (Dihydrotestosterone) in the Brain

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Many bodybuilders and fitness enthusiasts are going to be thrilled to find out how exactly DHT works in the Brain. What does it do for us there ? Is it really responsible for libido, and if so, what other chemicals does it affect? This article aims to surpass and explain the general knowledge floating around on the Internet and on Forums. I am not a doctor, but I have compiled a nice bunch of references and studies to cite the foundation of this article. I also will explain briefly (an estimate) how someone would feel based on the relative changes due to DHT - discussed in this article.

First off, a basic explanation of DHT (Dihydrotestosterone); it is an androgen (male sex hormone), like Testosterone, which rather than promoting the growth of muscle mass directly (tissue-acting), it acts via intracellular (in the cell) mechanisms to increase strength and metabolism. DHT is not very anabolic, but it is Androgenic, and thus meaning, it promotes masculine characteristics (such as a deeper voice, and growth of facial hair, body hair etc) (1).  DHT has a bad rap, since it has been claimed to cause an enlarged prostate, but if you follow the source, *most* of the studies saying this are linked to pharmaceutical promotion of their anti-prostate, anti-Male drug, Finasteride (Propecia) and Dustasteride(2) (3).  DHT has also been claimed to cause your hair follicles to become thin, and your hair - subsequently falls out. No. Just No. DHT has been implicated as a factor at most, more studies show that more specifically it is Zinc deficiency AND genetics that provoke male pattern baldness (4)(5).  Although Zinc deficiency causes the rise of DHT levels, it also causes increases in prolactin, and estrogen, thus the real problem here *could* have to do with either of those hormones. Just to clarify, Anti-ESTROGEN drugs have been used recently to treat prostate enlargement (BPH), and they are very successful, with less side-effects(6) (7) (8) (9). So if they were wrong about DHT causing prostate enlargement, maybe they were wrong about DHT and hair loss too.

      DHT - HOW IT AFFECTS THE BRAIN - AND NERVOUS SYSTEM


But anyway, we got carried away. Let's go on to discuss DHT's effects in the Brain.
DHT has pronounced effects on neurochemistry (it affects neurotransmitters in the brain). DHT has been shown to increase circulating epinephrine levels (adrenaline), this can cause anxiety in predisposed individuals, however, most of the time, this is not the case, since DHT also increases GABA activity in the brain, which is relaxing (10) (11) (12).   So in other words, DHT should promote A focused, calm burst of energy, which is what many users of DHT-based steroids, report as the "alpha-male" feeling (13) (14).  Dihydrotestosterone increase central and nervous system energy production by increasing not just adrenaline, but cyclic AMP (15). This molecule increase thermogenesis (fat-burning and heat production)(16).  Cyclic AMP facilitates the conversion of TSH thyroid hormone, to T4, a more potent thyroid hormone, thus, indirectly, DHT increases thyroid function (by increasing cyclic AMP) (17).

So seeing all this, DHT definitely acts as a nervous system stimulant, and a metabolic "probe", it also increases GABA.  Second to this though, it could indirectly decrease serotonin or serotonin receptors; since DHT antagonizes estrogen activity, and estrogen helps maintain the expression of serotonin receptors in the brain(18) (19). This is also consistent with DHT being shown to stop estrogen induced prolactin release(20). 
This is part of the reason behind using DHT Gel to treat gynecomasita.  Clearly DHT has anti-depressant effects, since Finasteride causes depression (21) and also based on the above mentioned activity of DHT in the brain. It gives energy, it gives focus, it gives aggression. 

DHT also improves spatial working memory(22), according to some studies, by altering NMDA-receptors(23) (namely increasing), and by improving Calcium-induced acetylcholine release & function in the hippocampus(24)(25); a very important area of the brain involved in memory formation and spatial (directional) memory.

DHT also decreases glutamate levels and excitory outputs through other mechanisms (26) (27) (28).


Finally, Dihydrotestosterone, or it's metabolite 3-alpha-Diol; downregulate alpha-adrenergic receptor distribution, leading to more inhibitory adrenergic (adrenaline influence)(29) (30) (31). For those who don't know, adrenaline can activate an 'alpha receptor' - which stimulates the nervous system, vasoconstricting blood vessels and arteries, raising blood pressure, or it can activate a beta-adrenergic receptor, generally vasodilating artieries, but yet, increasing heart contractile force. This all might just be another result or a reflection of what is mentioned above, that DHT increases epinephrine, GABA, and cyclic AMP.  However, in a separate study, Testosterone (without specificity), had upregulated alpha-1-receptors to protect the heart against ischemia(32).  Is this an effect of Testosterone or it's metabolites though. Likely, it doesn't matter, it was probably case coincidental, but may indicate that if blood pressure falls too low, Testosterone can increase it to maintain homeostasis.

In yet another study however, DHT has been shown to increase alpha-1-adrenergic expression, whereas Estrogen decreased the expression/density(33).
This again reflects the need for DHT and Estrogen to be kept in balance, as both promote vasodilation through different pathways, however, since Alpha-1-receptors are incredibly potent Vasoconstrictors, DHT + an OVERALL deficiency in nitric oxide may actually promote high blood pressure, especially in coordination with estrogen deficiency. Interestingly, Alpha-1-receptor activation may increase serotonin activity at the 5-HT1A receptor(34)(35), this is an auto-receptor that ironically seems to possess anxiolytic (serotonin-typical) effects. 5-HT1A activation has shown to help social anxiety disorder, but worsen anticipation anxieties(36)(37).
In another study, DHT/Androgens also facilitated serotonin 5-HT1A/1B agonist-decreases in aggression, which is controversial, although it appears that estrogen allows for intermale aggression by downregulating serotonin 5-HT1A/1B activity(38)(39). Thus DHT's only pro-aggressive propertly lies in it's adrenaline promoting effect, and not with serotonin.

      OTHER CENTRAL AND MOLECULAR CHANGES INDUCED BY DIHYDROTESTOSTERONE

1. Dihydrotestosterone appears to strongly increase MAPK; Mitogen-Activated-Protein-Kinase - this leads to a plethora of central and molecular changes as well as genomic/expressional changes(40)(41).
2. This action further reinforces and validates DHT's suppressive effects on serotonin systems (42) since activating MAPK leads to increased serotonin transporter (SERT) activity - an effect directly opposite of SSRI's (43) (44) (45)

So DHT via multiple pathways increases nervous system strength, DHT increases epinephrine levels, decreases prolactin (assuming you have enough dopamine production as well), increases GABA, may decrease serotonin and serotonin receptors. All-round this means DHT has positive effects on your chemistry and nerve cells. By reducing prolactin, and estrogen, and subsequently serotonin, and also regulating catecholamines, by this, DHT can definitely increase libido, and alleviate sexual anxiety in most individuals by increasing GABA. DHT is key to many of Testosterone's brain benefits. Keep in mind though, despite positive effects on brain chemistry, this still doesn't give an excuse to OD on aromatase inhibitors, likely, because you need a little bit of estrogen (not much at all), to promote nNOS (neuronal nitric oxide synthase) production. So DHT serves as a great compliment to a little bit of brain estradiol, and a great ratio of DHT to estrogen means optimal sex drive, stamina, charisma and general masculinity.


Let's summarize in Bullets Here.

• DHT regulates alpha and beta adrenergic receptors.
• DHT may increase alpha-1-receptor density.
• DHT may decrease glutamate activity and increases mGLU7 expression (which increases GABA release)
• DHT increases serotonin 5-HT1A receptor density by influencing A1-Adr.Receptors.
• DHT promotes serotonin 5-HT1A/1B activity and may reduce aggression in the presence of serotonin. Although this may easily be over ridden by the pro-adrenergic effects of DHT.
• DHT increases beta-endorphin release by ^ 5-HT1A receptor indirect activation.
• DHT facilitates the release of Epinephrine (adrenaline).
• DHT increases cyclic AMP.
• DHT blocks estrogen-induced prolactin release.
• DHT reduces serotonin and serotonin receptors by inhibiting estrogen influence in the Brain. (but mainly acting to oppose 5-HT2A,2C and 5-HT4 receptors)
• DHT increases Mitogen-Activated-Protein Kinase (MAPK) which leads to a variety of molecular changes and genomic changes as well as neural-changes; decreased serotonin activity in the brain and periphery. 
• DHT increases GABA and GABA-A (neurosteroid-specific) receptor expression. 
• DHT increases NMDA-receptors in the Hippocampus.
• DHT increases Ca3 (Calcium) evoked Acetylcholine Function(AcH release).
• DHT increases nervous system strength and regulates blood pressure.

This article has been Written BY : AMxProd    & Reviewed by  : D.Shiva
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