Editing Aggression (section)

====Effects on the nervous system====
[[File:Testosterone estradiol conversion.png|thumb|left|Testosterone to Estradiol conversion]]
Another line of research has focused on the proximate effects of circulating testosterone on the nervous system, as mediated by local metabolism within the brain. Testosterone can be metabolized to [[estradiol]] by the enzyme [[aromatase]], or to [[dihydrotestosterone]] (DHT) by [[5α-reductase]].<ref name="Soma2008" />

Aromatase is highly expressed in regions involved in the regulation of aggressive behavior, such as the amygdala and hypothalamus. In studies using genetic knockout techniques in inbred mice, male mice that lacked a functional aromatase enzyme displayed a marked reduction in aggression. Long-term treatment with estradiol partially restored aggressive behavior, suggesting that the neural conversion of circulating testosterone to estradiol and its effect on [[estrogen receptor]]s influences inter-male aggression. In addition, two different estrogen receptors, [[ERα]] and [[ERβ]], have been identified as having the ability to exert different effects on aggression in mice. However, the effect of estradiol appears to vary depending on the strain of mouse, and in some strains it reduces aggression during long days (16 h of light), while during short days (8 h of light) estradiol rapidly increases aggression.<ref name="Soma2008">{{cite journal |doi=10.1016/j.yfrne.2007.12.003 |pmid=18280561 |title=Novel mechanisms for neuroendocrine regulation of aggression |journal=[[Frontiers in Neuroendocrinology]] |volume=29 |issue=4 |pages=476–89 |year=2008 |last1=Soma |first1=Kiran K. |last2=Scotti |first2=Melissa-Ann L. |last3=Newman |first3=Amy E.M. |last4=Charlier |first4=Thierry D. |last5=Demas |first5=Gregory E. |s2cid=32650274 }}</ref>

Another hypothesis is that testosterone influences brain areas that control behavioral reactions. Studies in animal models indicate that aggression is affected by several interconnected cortical and subcortical structures within the so-called [[social behavior]] network. A study involving lesions and electrical-chemical stimulation in rodents and cats revealed that such a neural network consists of the medial [[amygdala]], medial [[hypothalamus]] and [[periaqueductal grey]] (PAG), and it positively modulates reactive aggression.<ref>{{cite journal |doi=10.2174/157015907780866929 |pmid=18615178 |pmc=2435345 |title=The Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders |journal=[[Current Neuropharmacology]] |volume=5 |issue=2 |pages=135–47 |year=2007 |last1=Siegel |first1=Allan |last2=Bhatt |first2=Suresh |last3=Bhatt |first3=Rekha |last4=Zalcman |first4=Steven }}</ref> Moreover, a study done in human subjects showed that prefrontal-amygdala connectivity is modulated by endogenous testosterone during social emotional behavior.<ref>{{cite journal |doi=10.1093/cercor/bhr001 |pmid=21339377 |pmc=3169658 |title=Endogenous Testosterone Modulates Prefrontal-Amygdala Connectivity during Social Emotional Behavior |journal=[[Cerebral Cortex (journal)|Cerebral Cortex]] |volume=21 |issue=10 |pages=2282–90 |year=2011 |last1=Volman |first1=I. |last2=Toni |first2=I. |last3=Verhagen |first3=L. |last4=Roelofs |first4=K. }}</ref>

In human studies, testosterone-aggression research has also focused on the role of the [[orbitofrontal cortex]] (OFC). This brain area is strongly associated with impulse control and self-regulation systems that integrate emotion, motivation, and cognition to guide context-appropriate behavior.<ref name="Mehta, P. H., Beer, J. 2009 2357–2368">{{cite journal |doi=10.1162/jocn.2009.21389 |pmid=19925198 |title=Neural Mechanisms of the Testosterone–Aggression Relation: The Role of Orbitofrontal Cortex |journal=[[Journal of Cognitive Neuroscience]] |volume=22 |issue=10 |pages=2357–68 |year=2010 |last1=Mehta |first1=Pranjal H. |last2=Beer |first2=Jennifer |citeseerx=10.1.1.518.2751 |s2cid=710598 }}</ref> Patients with localized lesions to the OFC engage in heightened reactive aggression.<ref>{{cite journal |doi=10.1176/appi.ajp.2008.07111774 |pmid=18346997 |pmc=4176893 |title=Neurobiology of Aggression and Violence |journal=[[American Journal of Psychiatry]] |volume=165 |issue=4 |pages=429–42 |year=2008 |last1=Siever |first1=Larry J. }}</ref> Aggressive behavior may be regulated by testosterone via reduced medial OFC engagement following social provocation.<ref name="Mehta, P. H., Beer, J. 2009 2357–2368"/> When measuring participants' salivary testosterone, higher levels can predict subsequent aggressive behavioral reactions to unfairness faced during a task. Moreover, brain scanning with [[fMRI]] shows reduced activity in the medial OFC during such reactions. Such findings may suggest that a specific brain region, the OFC, is a key factor in understanding reactive aggression.