Editing Androgen insensitivity syndrome (section)

===Androgens and the androgen receptor===
{{Main|Androgen receptor}}
The [[Androgen#Functions|effects]] that [[androgens]] have on the human body ([[Puberty#Physical changes in boys|virilization]], masculinization, [[anabolism]], etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body.<ref name="1998 wang 83" />  Likewise, the androgen receptor itself is generally inactive in the cell until androgen binding occurs.<ref name="1995 quigley 16" />

The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects:<ref name="2006 hughes 20" /><ref name="2008 galani 7" /><ref name="1995 quigley 16" /><ref name="2005 gottlieb 10" />

{{ordered list
 | Androgen enters the cell.
  {{ordered list|type=lower-alpha
    | Only certain organs in the body, such as the [[gonads]] and the [[adrenal glands]], produce the androgen [[testosterone]].
    | Testosterone is converted into [[dihydrotestosterone]], a chemically similar androgen, in cells containing the [[enzyme]] [[5-alpha reductase]].
    | Both androgens exert their influence through binding with the androgen receptor.
  }}
 | Androgen binds with the androgen receptor.
  {{ordered list|type=lower-alpha
    | The androgen receptor is expressed ubiquitously throughout the tissues of the human body.
    | Before it binds with an androgen, the androgen receptor is bound to [[heat shock proteins]].
    | These heat shock proteins are released upon androgen binding.
    | Androgen binding induces a stabilizing, [[Chemical structure|conformational]] change in the androgen receptor.
    | The two [[zinc fingers]] of the [[DNA-binding domain]] are exposed as a result of this new conformation.
    | AR stability is thought to be aided by type II [[Transcription coregulator|coregulators]], which modulate [[protein folding]] and androgen binding, or facilitate NH2/carboxyl-terminal interaction.
  }}
 | The hormone-activated androgen receptor is [[Protein phosphorylation|phosphorylated]].
  {{ordered list|type=lower-alpha
    | Receptor phosphorylation can occur before androgen binding, although the presence of androgen promotes hyperphosphorylation.
    | The biological ramifications of receptor phosphorylation are unknown.
  }}
 | The hormone-activated androgen receptor [[Protein targeting#Protein translocation|translocates]] to the nucleus.
  {{ordered list|type=lower-alpha
    | Nucleocytoplasmic transport is in part facilitated by an [[amino acid]] [[Nucleic acid sequence|sequence]] on the [[androgen receptor|AR]] called the [[nuclear localization signal]].
    | The AR's nuclear localization signal is primarily encoded in the hinge region of the AR gene.
  }}
 | [[Protein dimer|Homodimerization]] occurs.
  {{ordered list|type=lower-alpha
    | Dimerization is mediated by the second (nearest the 3' end) [[zinc finger]].
  }}
 | DNA binding to regulatory [[Hormone response element|androgen response elements]] occurs.
  {{ordered list|type=lower-alpha
    | Target genes contain (or are flanked by) [[Transcription (genetics)|transcriptional]] enhancer nucleotide sequences that interact with the first zinc finger.
    | These areas are called androgen response elements.
  }}
 | [[Coactivator (genetics)|Coactivators]] are recruited by the AR.
  {{ordered list|type=lower-alpha
    | Type I coactivators (i.e., coregulators) are thought to influence AR transcriptional activity by facilitating DNA occupancy, [[chromatin remodeling]], or the recruitment of general [[transcription factor]]s associated with [[RNA polymerase II]] holocomplex.
  }}
 | Target [[gene transcription]] ensues.
}}

In this way, androgens bound to androgen receptors [[Regulation of gene expression|regulate the expression]] of target genes, thus produce androgenic effects.<ref>{{Cite journal |last1=Jin |first1=Hong-Jian |last2=Kim |first2=Jung |last3=Yu |first3=Jindan |date=September 2013 |title=Androgen receptor genomic regulation |url=https://tau.amegroups.com/article/view/2705 |journal=Translational Andrology and Urology |language=en |volume=2 |issue=3 |pages=15877–15177 |doi=10.3978/j.issn.2223-4683.2013.09.01 |issn=2223-4691 |pmc=4165347 |pmid=25237629}}</ref>

Theoretically, certain mutant androgen receptors can function without androgens; ''in vitro'' studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted.<ref name="1991 jenster 5" /><ref name="1991 simental 266" />  Conversely, the steroid-binding domain may act to repress the AR [[transactivation]] domain, perhaps due to the AR's [[Ligand (biochemistry)|unliganded]] conformation.<ref name="1995 quigley 16" />

[[File:Human sexual differentiation.gif|thumb|Sexual differentiation: The human embryo has indifferent sex accessory ducts until the seventh week of development.<ref name="2000 gilbert" />]]