title: Suprachiasmatic nucleus as the site of androgen action on circadian rhythms.
abstract: Androgens act widely in the body in both central and peripheral sites. Prior studies indicate that in the mouse, suprachiasmatic nucleus (SCN) cells bear androgen receptors (ARs). The SCN of the hypothalamus in mammals is the locus of a brain clock that regulates circadian rhythms in physiology and behavior. Gonadectomy results in reduced AR expression in the SCN and in marked lengthening of the period of free-running activity rhythms. Both responses are restored by systemic administration of androgens, but the site of action remains unknown. Our goal was to determine whether intracranial androgen implants targeted to the SCN are sufficient to restore the characteristic free-running period in gonadectomized male mice. The results indicate that hypothalamic implants of testosterone propionate in or very near the SCN produce both anatomical and behavioral effects, namely increased AR expression in the SCN and restored period of free-running locomotor activity. The effect of the implant on the period of the free-running locomotor rhythm is positively correlated with the amount of AR expression in the SCN. There is no such correlation of period change with amount of AR expression in other brain regions examined, namely the preoptic area, bed nucleus of the stria terminalis and premammillary nucleus. We conclude that the SCN is the site of action of androgen effects on the period of circadian activity rhythmicity.
authors.affiliation: Department of Psychology, Barnard College, New York, NY, USA. Electronic address: model.zina@gmail.com.
authors.forename: Zina
authors.initials: Z
authors.lastname: Model
authors.affiliation: Department of Psychology, Columbia University, New York, NY, USA. Electronic address: butlema@ohsu.edu.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Butler
authors.affiliation: Department of Psychology, Barnard College, New York, NY, USA; Department of Psychology, Columbia University, New York, NY, USA. Electronic address: jlesauter@barnard.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: LeSauter
authors.affiliation: Department of Psychology, Barnard College, New York, NY, USA; Department of Psychology, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. Electronic address: Rae.Silver@columbia.edu.
authors.forename: Rae
authors.initials: R
authors.lastname: Silver
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009919:Orchiectomy; D011944:Receptors, Androgen / Q000378:metabolism; D012420:Running; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000728:Androgens; D011944:Receptors, Androgen
keywords: Androgen receptor; Brain clock; Free-running period; Hypothalamus; Light; Locomotor activity; Sex difference; Sex steroid; Testosterone