Androgens modulate structure and function of the suprachiasmatic nucleus brain clock
Open accessAbstract
Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is unexplored. In the present study, we ask whether androgens influence the structure and function of the mouse SCN by examining the effects of gonadectomy (GDX) on the structure of the SCN circuit and its responses to light, including induction of clock genes and behavioral phase shifting. We found that after GDX, glial fibrillary acidic protein increased with concomitant decreases in the expression of the synaptic proteins synaptophysin and postsynaptic density 95. We also found that GDX exerts effects on the molecular and behavioral responses to light that are phase dependent. In late night [circadian time (CT)21], GDX increased light-induced mPer1 but not mPer2 expression compared with intact (INT) controls. In contrast, in early night (CT13.5), GDX decreased light induced mPer2 but had no effect on mPer1. At CT13.5, GDX animals also showed larger phase delays than did INT. Treatment of GDX animals with the nonaromatizable androgen dihydrotestosterone restored glial fibrillary acidic protein, postsynaptic density 95, and synaptophysin in the SCN and reinstated the INT pattern of molecular and behavioral responses to light. Together, the results reveal a role for androgens in regulating circuitry in the mouse SCN, with functional consequences for clock gene expression and behavioral responses to photic phase resetting stimuli.
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Both androgens and estrogens can activationally alter photic sensitivity within the entrainment pathway, as measured by the induction of FOS and clock genes (Per1, Per2).
“For example, both androgens and estrogens can activationally alter photic sensitivity within the entrainment pathway, as measured by the induction of immediate early gene expression (FOS) and clock genes (Per1, Per2, [3, 88, 90]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [88]
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Cites
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
A marker for the end of adolescence
Roenneberg, T., Kuehnle, T., Pramstaller, P. P., Ricken, J., Havel, M., Guth, A., & Merrow, M. (2004) · Current Biology · doi:10.1016/j.cub.2004.11.039 · Cited by 1,585 · see citing works
(2009) · Elsevier eBooks · doi:10.1016/c2009-1-03789-7 · Cited by 1,543 · see citing works
Suprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216 · see citing works
Shigeyoshi, Y., Taguchi, K., Yamamoto, S., Takekida, S., Yan, L., Tei, H., Moriya, T., Shibata, S., Loros, J. J., Dunlap, J. C., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80494-8 · Cited by 891 · see citing works
Abrahamson, E. E., & Moore, R. Y. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02890-6 · Cited by 788 · see citing works
New roles for astrocytes: Regulation of synaptic transmission
Newman, E. A. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00237-6 · Cited by 619 · see citing works
Activity-dependent structural and functional plasticity of astrocyte-neuron interactions
Theodosis, D. T., Poulain, D. A., & Oliet, S. H. R. (2008) · Physiological Reviews · doi:10.1152/physrev.00036.2007 · Cited by 531 · see citing works
Non-genomic actions of androgens
Foradori, C. D., Weiser, M. J., & Handa, R. J. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.10.005 · Cited by 493 · see citing works
Orchestrating time: arrangements of the brain circadian clock
Antle, M. C., & Silver, R. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.01.003 · Cited by 463 · see citing works
Self-citationThe hypothalamic suprachiasmatic nucleus of rat: Intrinsic anatomy
van den Pol, A. N. (1980) · The Journal of comparative neurology · doi:10.1002/cne.901910410 · Cited by 447 · see citing works
Androgens Regulate the Dendritic Length of Mammalian Motoneurons in Adulthood
Kurz, E. M., Sengelaub, D. R., & Arnold, A. P. (1986) · Science · doi:10.1126/science.3961488 · Cited by 380 · see citing works
Estradiol shortens the period of hamster circadian rhythms
Morin, L. P., Fitzgerald, K. M., & Zucker, I. (1977) · Science · doi:10.1126/science.557840 · Cited by 350 · see citing works
Activity-dependent structural plasticity
Butz, M., Wörgötter, F., & van Ooyen, A. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.023 · Cited by 321 · see citing works
Temporal Precision in the Mammalian Circadian System: A Reliable Clock from Less Reliable Neurons
Herzog, E. D., Aton, S. J., Numano, R., Sakaki, Y., & Tei, H. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730403260776 · Cited by 281 · see citing works
Akiyama, M., Kouzu, Y., Takahashi, S., Wakamatsu, H., Moriya, T., Maetani, M., Watanabe, S., Tei, H., Sakaki, Y., & Shibata, S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-03-01115.1999 · Cited by 264 · see citing works
Calcium excitability and oscillations in suprachiasmatic nucleus neurons and glia in vitro
van den Pol, A. N., Finkbeiner, S., & Cornell-Bell, A. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02648.1992 · Cited by 252 · see citing works
Paus, T., Otaky, N., Caramanos, Z., MacDonald, D. J., Zijdenbos, A. P., d'Avirro, D., Gutmans, D. S., Holmes, C. J., Tomaiuolo, F., & Evans, A. C. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19961223)376:4 · Cited by 228 · see citing works
Two distinct oscillators in the rat suprachiasmatic nucleus in vitro.
Shinohara, K., Honma, S., Katsuno, Y., Abe, H., & Honma, K.-I. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7396 · Cited by 215 · see citing works
Yan, L., & Silver, R. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02224.x · Cited by 208 · see citing works
Self-citationDaan, S., Damassa, D., Pittendrigh, C. S., & Smith, E. R. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3744 · Cited by 207 · see citing works
Excitation control: balancing PSD-95 function at the synapse
Keith, D. J. (2008) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.004.2008 · Cited by 206 · see citing works
Léránth, C., Hajszán, T., & MacLusky, N. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4516-03.2004 · Cited by 206 · see citing works
Zhou, L., Blaustein, J. D., & De Vries, G. J. (1994) · Endocrinology · doi:10.1210/endo.134.6.8194487 · Cited by 189 · see citing works
Receptors for neurotransmitters on astrocytes in the mammalian central nervous system
Hösli, E., & Hösli, L. (1993) · Progress in Neurobiology · doi:10.1016/0301-0082(93)90019-o · Cited by 178 · see citing works
Lindzey, J. K., Wetsel, W. C., Couse, J. F., Stoker, T. E., Cooper, R. L., & Korach, K. S. (1998) · Endocrinology · doi:10.1210/endo.139.10.6253 · Cited by 165 · see citing works
Diurnal Sex Differences in the Sleep-Wake Cycle of Mice are Dependent on Gonadal Function
Paul, K. N., Dugovic, C., Turek, F. W., & Laposky, A. D. (2006) · SLEEP · doi:10.1093/sleep/29.9.1211 · Cited by 159 · see citing works
Hannibal, J., Jamen, F., Nielsen, H. S., Journot, L., Brabet, P., & Fahrenkrug, J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04883.2001 · Cited by 158 · see citing works
Steroid hormones as mediators of neural plasticity
McEwen, B. S., Coirini, H., Westlind-Danielsson, A., Frankfurt, M., Gould, E., Schumacher, M., & Woolley, C. (1991) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(91)90067-f · Cited by 136 · see citing works
A role for androgens in regulating circadian behavior and the suprachiasmatic nucleus
Karatsoreos, I. N., Wang, A., Sasanian, J., & Silver, R. (2007) · Endocrinology · doi:10.1210/en.2007-0775 · Cited by 136 · see citing works
Self-citationIwahana, E., Karatsoreos, I., Shibata, S., & Silver, R. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.11.014 · Cited by 127 · see citing works
Self-citationDay, J. R., Laping, N. J., McNeill, T. H., Schreiber, S. S., Pasinetti, G. M., & Finch, C. E. (1990) · Molecular Endocrinology · doi:10.1210/mend-4-12-1995 · Cited by 113 · see citing works
Exploring Spatiotemporal Organization of SCN CircuitsPreprint
Yan, L., Karatsoreos, I. N., LeSauter, J., Welsh, D. K., Kay, S. A., Foley, D. K., & Silver, R. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.037 · Cited by 112 · see citing works
Self-citationVida, B., Hrabovszky, E., Kalamatianos, T., Coen, C. W., Liposits, Z., & Kalló, I. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01787.x · Cited by 108 · see citing works
Karatsoreos, I. N., & Silver, R. (2007) · Endocrinology · doi:10.1210/en.2007-1083 · Cited by 101 · see citing works
Glial modulation of synaptic transmission: Insights from the supraoptic nucleus of the hypothalamus
Oliet, S. H. R., Piet, R., Poulain, D. A., & Theodosis, D. T. (2004) · Glia · doi:10.1002/glia.20032 · Cited by 98 · see citing works
Morin, L. P., & Cummings, L. A. (1981) · Physiology & Behavior · doi:10.1016/0031-9384(81)90106-2 · Cited by 93 · see citing works
Effect of ovarian hormones on synchrony of hamster circadian rhythms
Morin, L. P. (1980) · Physiology & Behavior · doi:10.1016/0031-9384(80)90406-0 · Cited by 92 · see citing works
Sex differences in human circadian rhythms: Intrinsic periods and sleep fractions
Wever, R. A. (1984) · Cellular and Molecular Life Sciences · doi:10.1007/bf01946652 · Cited by 90 · see citing works
MacLusky, N. J., Hajszán, T., & Léránth, C. (2004) · Endocrinology · doi:10.1210/en.2004-0477 · Cited by 89 · see citing works
Antle, M. C., Kriegsfeld, L. J., & Silver, R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4696-04.2005 · Cited by 85 · see citing works
Self-citationHajszán, T., MacLusky, N. J., Johansen, J. A., Jordan, C. L., & Léránth, C. (2007) · Endocrinology · doi:10.1210/en.2006-1626 · Cited by 84 · see citing works
CELLULAR COMMUNICATION AND COUPLING WITHIN THE SUPRACHIASMATIC NUCLEUS
Michel, S. H., Colwell, C. S., & Colwell, C. S. (2001) · Chronobiology International · doi:10.1081/cbi-100106074 · Cited by 74 · see citing works
Photic Entrainment ofPeriodMutant Mice is Predicted from Their Phase Response Curves
Pendergast, J. S., Friday, R. C., & Yamazaki, S. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2607-10.2010 · Cited by 73 · see citing works
Rieux, C., Carney, R. M., Lupi, D., Dkhissi‐Benyahya, O., Jansen, K., Chounlamountri, N., Foster, R. G., & Cooper, H. M. (2002) · Journal of Biological Rhythms · doi:10.1177/074873002129002410 · Cited by 64 · see citing works
Influence of Sex on Sleep Regulatory Mechanisms
Paul, K. N., Turek, F. W., & Kryger, M. H. (2008) · Journal of Women's Health · doi:10.1089/jwh.2008.0841 · Cited by 63 · see citing works
Diurnal regulation of the gastrin‐releasing peptide receptor in the mouse circadian clock
Karatsoreos, I. N., Romeo, R. D., McEwen, B. S., et al. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04633.x · Cited by 63 · see citing works
Self-citationAchermann, P., & Kunz, H. (1999) · Journal of Biological Rhythms · doi:10.1177/074873099129001028 · Cited by 61 · see citing works
MacLusky, N. J., Hajszán, T., Johansen, J. A., Jordan, C. L., & Leranth, C. (2006) · Endocrinology · doi:10.1210/en.2005-0673 · Cited by 59 · see citing works
Melcangi, R. C., Riva, M. A., Furnagalli, F., et al. (1996) · Brain Research · doi:10.1016/0006-8993(95)01302-4 · Cited by 55 · see citing works
Hummer, D. L., Jechura, T. J., Mahoney, M. M., & Lee, T. M. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00043.2006 · Cited by 52 · see citing works
Shinohara, K., Funabashi, T., Mitushima, D., & Kimura, F. (2000) · Neuroscience Research · doi:10.1016/s0168-0102(00)00141-3 · Cited by 50 · see citing works
Effects of sex steroids on sleep
Empson, J., & Purdie, D. W. (1999) · Annals of Medicine · doi:10.3109/07853899708998790 · Cited by 49 · see citing works
Girardet, C., Blanchard, M., Ferracci, G., Lévêque, C., Moreno, M., François‐Bellan, A., Becquet, D., & Bosler, O. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.07071.x · Cited by 48 · see citing works
Romeo, R. D., Karatsoreos, I. N., Jasnow, A. M., & McEwen, B. S. (2007) · Neuroendocrinology · doi:10.1159/000102950 · Cited by 48 · see citing works
Self-citationLavialle, M., Bègue, A.-L., Papillon, C., & Vilaplana, J. (2001) · Glia · doi:10.1002/glia.1044 · Cited by 45 · see citing works
Butler, M. P., & Silver, R. (2009) · Journal of Biological Rhythms · doi:10.1177/0748730409344800 · Cited by 41 · see citing works
Self-citationTesticular hormones modulate circadian rhythms of the diurnal rodent, Octodon degus
Jechura, T. J., Walsh, J. M., & Lee, T. M. (2000) · Hormones and Behavior · doi:10.1006/hbeh.2000.1624 · Cited by 40 · see citing works
Pubertal Development of Sex Differences in Circadian Function: An Animal Model
Lee, T. M., Hummer, D. L., Jechura, T. J., & Mahoney, M. M. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.031 · Cited by 40 · see citing works
Chapter 5 Astrocytes in the mammalian circadian clock: putative roles
Serviere, J., & Lavialle, M. (1996) · Progress in brain research · doi:10.1016/s0079-6123(08)60400-8 · Cited by 37 · see citing works
Pak, T. R., Chung, W. C. J., Hinds, L. R., & Handa, R. J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00037.2009 · Cited by 25 · see citing works
Testosterone Suppresses Circadian Responsiveness to Social Cues in the Diurnal Rodent Octodon degus
Jechura, T. J., Walsh, J. M., & Lee, T. M. (2003) · Journal of Biological Rhythms · doi:10.1177/0748730402239675 · Cited by 23 · see citing works
Circadian Regulation of Endocrine Functions
Butler, M. P., Kriegsfeld, L. J., & Silver, R. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00013-9 · Cited by 22 · see citing works
Self-citationMattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1
Flagged first, then by citations
Research works printed but not linked: 3
- [7]7. Fernández-Guasti A, Kruijver FP, Fodor M, Swaab DF. 2000. Sex differences in the distribution of androgen receptors in the human hypothalamus. J Comp Neurol 425:422–435 [DOI] [PubMed] [Google Scholar]
- [8]8. Kashon ML, Arbogast JA, Sisk CL. 1996. Distribution and hormonal regulation of androgen receptor immunoreactivity in the forebrain of the male European ferret. J Comp Neurol 376:567–586 [DOI] [PubMed] [Google Scholar]
- [36]36. Lu B, Chow A. 1999. Neurotrophins and hippocampal synaptic transmission and plasticity. J Neurosci Res 58:76–87 [PubMed] [Google Scholar]
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Mong, J. A., Baker, F. C., Mahoney, M. M., Paul, K. N., Schwartz, M. D., Semba, K., & Silver, R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4175-11.2011 · Cited by 295 · see citing works
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- Authors
- Karatsoreos, I. N., Butler, M. P., LeSauter, J., & Silver, R.
- Affiliations
- Columbia University (US)
- Barnard College (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Silver, Rae
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2011-03-01
- Volume
- 152
- Issue
- 5
- Pages
- 1970-1978
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3075936
- OpenAlex
- W2132941085
- Cited by
- 97
- References
- 65
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 19 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 8 · 2013: 8 · 2012: 5
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007328)
- National Institute of Neurological Disorders and Stroke (NS-37919, R01NS037919)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- androgens, suprachiasmatic nucleus, circadian clock, gonadectomy, androgen receptor, dihydrotestosterone, clock genes, mPer1, mPer2, light-induced phase shift, phase resetting, glial fibrillary acidic protein, synaptophysin, PSD-95, synaptic proteins, neuroplasticity, gonadal hormones
- MeSH terms
- Disks Large Homolog 4 Protein, Androgens, Animals, Biological Clocks, Brain, Circadian Rhythm, Glial Fibrillary Acidic Protein, Light, Male, Membrane Proteins, Mice, Inbred C57BL, Motor Activity, Orchiectomy, Dihydrotestosterone, Suprachiasmatic Nucleus, Time Factors, Blotting, Western, Gene Expression, Synaptophysin, In Situ Hybridization, Microscopy, Confocal, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases, Period Circadian Proteins
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