Editing Testosterone (section)

===Neurosteroid activity===
Testosterone, via its [[active metabolite]] [[3α-androstanediol]], is a potent [[positive allosteric modulator]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]].<ref name="KohtzFrye2012">{{cite book | vauthors = Kohtz AS, Frye CA | chapter = Dissociating Behavioral, Autonomic, and Neuroendocrine Effects of Androgen Steroids in Animal Models | title = Psychiatric Disorders | series = [[Methods in Molecular Biology]] | volume = 829 | pages = 397–431 | year = 2012 | publisher = Springer | pmid = 22231829 | doi = 10.1007/978-1-61779-458-2_26 | isbn = 978-1-61779-457-5 }}</ref>

Testosterone has been found to act as an [[receptor antagonist|antagonist]] of the [[TrkA]] and [[p75NTR|p75<sup>NTR</sup>]], [[receptor (biochemistry)|receptor]]s for the [[neurotrophin]] [[nerve growth factor]] (NGF), with high [[affinity (pharmacology)|affinity]] (around 5&nbsp;nM).<ref name="pmid26908835">{{cite journal | vauthors = Prough RA, Clark BJ, Klinge CM | title = Novel mechanisms for DHEA action | journal = J. Mol. Endocrinol. | volume = 56 | issue = 3 | pages = R139–55 | year = 2016 | pmid = 26908835 | doi = 10.1530/JME-16-0013 | doi-access = free }}</ref><ref name="pmid21541365">{{cite journal | vauthors = Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A | title = Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis | journal = PLOS Biol. | volume = 9 | issue = 4 | pages = e1001051 | year = 2011 | pmid = 21541365 | pmc = 3082517 | doi = 10.1371/journal.pbio.1001051 | doi-access = free }}</ref><ref name="pmid23074265">{{cite journal | vauthors = Gravanis A, Calogeropoulou T, Panoutsakopoulou V, Thermos K, Neophytou C, Charalampopoulos I | s2cid = 26914550 | title = Neurosteroids and microneurotrophins signal through NGF receptors to induce prosurvival signaling in neuronal cells | journal = Sci Signal | volume = 5 | issue = 246 | pages = pt8 | year = 2012 | pmid = 23074265 | doi = 10.1126/scisignal.2003387 }}</ref> In contrast to testosterone, DHEA and [[DHEA sulfate]] have been found to act as high-affinity [[agonist]]s of these receptors.<ref name="pmid26908835" /><ref name="pmid21541365" /><ref name="pmid23074265" />

Testosterone is an antagonist of the [[sigma-1 receptor]] (K<sub>i</sub> = 1,014 or 201&nbsp;nM).<ref name="AlbayrakHashimoto2017">{{cite book | vauthors = Albayrak Y, Hashimoto K | series = Advances in Experimental Medicine and Biology | title = Sigma Receptors: Their Role in Disease and as Therapeutic Targets | chapter = Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders | volume = 964 | pages = 153–161 | year = 2017 | publisher = Springer | pmid = 28315270 | doi = 10.1007/978-3-319-50174-1_11 | isbn = 978-3-319-50172-7 }}</ref> However, the concentrations of testosterone required for binding the receptor are far above even total circulating concentrations of testosterone in adult males (which range between 10 and 35&nbsp;nM).<ref name="Regitz-Zagrosek2012">{{cite book| vauthors = Regitz-Zagrosek V |title=Sex and Gender Differences in Pharmacology|url=https://books.google.com/books?id=J3VxihGDh9wC&pg=PA245|date=2 October 2012|publisher=Springer Science & Business Media|isbn=978-3-642-30725-6|pages=245–}}</ref>