title: A role for androgens in regulating circadian behavior and the suprachiasmatic nucleus.
abstract: The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock controlling behavioral and physiological rhythms, including rhythmic secretion of gonadal hormones. Gonadectomy results in marked alteration of circadian behaviors, including lengthened free-running period, decreased precision of daily onset of running, and elimination of early-evening but not late-night activity bouts. Androgen replacement restores these responses. These aspects of rhythmicity are thought to be regulated by the brain clock, although the site of androgen action remains unknown. Anatomically, the rodent SCN is composed of a ventrolateral core and a dorsomedial shell, and the present studies show that androgen receptors (AR) are localized to the ventrolateral core SCN. Using a transgenic mouse bearing dual reporter molecules driven by the AR targeted to both membrane and nucleus, we find that projections of AR-containing cells form a dense plexus in the core, with their fibers appearing to exit the SCN dorsally. In a second transgenic strain, in which the retinorecipient gastrin-releasing peptide cells express a green fluorescent protein reporter, we show that gastrin-releasing peptide cells contain AR. Through immunocytochemistry, we also show that SCN AR cells express FOS after a light pulse. Importantly, gonadectomy reduces the FOS response after a phase-shifting light pulse, whereas androgen replacement restores levels to those in intact animals. Taken together, the results support previous findings of a hypothalamic neuroendocrine feedback loop. As such, the SCN regulates circadian rhythms in gonadal hormone secretion, and in turn, androgens act on their receptors within the SCN to alter circadian function.
authors: Department of Psychology, Columbia University, New York, NY 10027, USA.
authors: Ilia N
authors: IN
authors: Karatsoreos
authors: Alice
authors: A
authors: Wang
authors: Jasmine
authors: J
authors: Sasanian
authors: Rae
authors: R
authors: Silver
mesh_terms: D000728:Androgens / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009919:Orchiectomy; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone
references: J Neurosci. 2003 Sep 3;23(22):8070-6
references: 12954869
references: Mol Endocrinol. 2003 Sep;17(9):1738-50
references: 12791770
references: Endocrine. 1999 Oct;11(2):137-43
references: 10709760
references: Science. 2000 Apr 28;288(5466):682-5
references: 10784453
references: Acta Ophthalmol Scand. 2000 Apr;78(2):146-53
references: 10794246
references: J Comp Neurol. 2000 Sep 25;425(3):422-35
references: 10972942
references: J Comp Neurol. 2004 Jan 12;468(3):361-79
references: 14681931
references: J Neurosci. 2004 Jan 7;24(1):68-75
references: 14715939
references: Biol Rev Camb Philos Soc. 2004 Feb;79(1):61-77
references: 15005173
references: Neurosci Biobehav Rev. 2004 Mar;28(1):55-63
references: 15036933
references: J Neurochem. 2004 Aug;90(4):769-75
references: 15287881
references: Neuron. 2004 Aug 5;43(3):313-9
references: 15294140
references: Proc Natl Acad Sci U S A. 1975 Sep;72(9):3744-7
references: 1059163
references: Q Rev Biol. 1979 Sep;54(3):265-99
references: 390600
references: Am J Physiol. 1980 Jan;238(1):R97-101
references: 7356053
references: Physiol Behav. 1981 May;26(5):825-38
references: 7267776
references: J Comp Neurol. 1982 Apr 10;206(3):273-7
references: 7085933
references: Am J Physiol. 1983 Jan;244(1):R93-105
references: 6849422
references: Sleep. 1984;7(1):27-51
references: 6718923
references: Experientia. 1984 Nov 15;40(11):1226-34
references: 6500007
references: Physiol Behav. 1985 Dec;35(6):985-92
references: 4095192
references: Physiol Behav. 1990 Sep;48(3):403-8
references: 2267249
references: Biol Reprod. 1990 Oct;43(4):586-91
references: 2289012
references: Endocrinology. 1994 Jun;134(6):2622-7
references: 8194487
references: Neuron. 1995 Apr;14(4):697-706
references: 7718233
references: Brain Res Dev Brain Res. 1995 Feb 16;84(2):278-81
references: 7743647
references: J Comp Neurol. 1996 Dec 23;376(4):567-86
references: 8978471
references: Prog Brain Res. 1996;111:103-19
references: 8990910
references: J Biol Rhythms. 1997 Apr;12(2):122-35
references: 9090566
references: Endocrinology. 1998 Apr;139(4):1594-601
references: 9528939
references: Endocrinology. 1998 Oct;139(10):4092-101
references: 9751487
references: Brain Res. 1999 Feb 20;819(1-2):23-32
references: 10082857
references: J Neuroendocrinol. 1999 Jul;11(7):481-90
references: 10444305
references: Curr Biol. 2004 Dec 29;14(24):R1038-9
references: 15620633
references: Trends Neurosci. 2005 Mar;28(3):145-51
references: 15749168
references: Nat Neurosci. 2005 Apr;8(4):476-83
references: 15750589
references: Mol Cell Endocrinol. 2005 May 31;236(1-2):1-7
references: 15876478
references: Nat Rev Genet. 2005 Jul;6(7):544-56
references: 15951747
references: J Neurochem. 2005 Sep;94(6):1639-51
references: 16011741
references: J Neurosci. 2005 Nov 30;25(48):11155-64
references: 16319315
references: Nature. 2005 Dec 22;438(7071):1095-6
references: 16371996
references: Eur J Neurosci. 2006 Feb;23(4):1047-53
references: 16519669
references: J Biol Rhythms. 2006 Dec;21(6):458-69
references: 17107936
references: J Biol Rhythms. 2007 Feb;22(1):3-13
references: 17229920
references: Curr Biol. 2007 Mar 6;17(5):468-73
references: 17320387
references: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7664-9
references: 17463091
references: J Biol Rhythms. 2001 Apr;16(2):105-16
references: 11302553
references: Eur J Neurosci. 2001 Aug;14(4):666-74
references: 11556891
references: J Neurosci. 2001 Oct 1;21(19):7742-50
references: 11567064
references: Brain Res. 2001 Oct 19;916(1-2):172-91
references: 11597605
references: Mol Pharmacol. 2002 Jan;61(1):26-34
references: 11752203
references: Ann N Y Acad Sci. 2001 Dec;949:44-57
references: 11795379
references: Eur J Neurosci. 2002 Apr;15(7):1153-62
references: 11982626
references: Neuroreport. 2002 May 7;13(6):857-60
references: 11997701
references: Eur J Neurosci. 2002 Oct;16(8):1531-40
references: 12405967
references: Endocrinology. 2003 Jan;144(1):230-9
references: 12488349
references: Eur J Neurosci. 2002 Dec;16(12):2469-74
references: 12492442
references: Endocrinology. 2003 May;144(5):2055-67
references: 12697714
references: Chronobiol Int. 2003 Mar;20(2):209-21
references: 12723881
references: Science. 2003 Nov 21;302(5649):1408-12
references: 14631044