Dose-dependent effects of androgens on the circadian timing system and its response to light

Matthew Butler, Ilia N. Karatsoreos, Joseph Le Sauter, Rae Silver

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The hypothalamic suprachiasmatic nucleus (SCN) is the locus of a master clock that regulates circadian rhythms in physiology and behavior. Gonadectomy in male mice lengthens the period of circadian rhythms and increases the day-to-day variability of activity onset time. Both of these responses are rescued by the nonaromatizable androgen dihydrotestosterone. Androgen receptors (AR) are localized in SCN neurons that receive direct retinal input. To explore how androgens affect circadian clock function and its responsiveness to photic cues, we measured wheel-running behavior and SCN AR expression in intact, gonadectomized, and testosterone-replaced mice, held under various photic conditions. Gonadectomy lengthened circadian period in constant dim light but not in constant darkness. Increasing intensities of constant light parametrically increased circadian period, and this was potentiated at all intensities by gonadectomy. In contrast, gonadectomy did not alter light-induced pupil constriction, suggesting a nonretinal locus of hormone action. In hormone-replaced animals housed in constant darkness, T concentration was positively correlated with precision of activity onset and with SCN AR expression and negatively correlated with duration of activity. We infer the existence of two androgenic mechanisms: one modulates SCN responsiveness to light, and the second modulates SCN timekeeping and locomotor activity in a dose-dependent manner. Finally, the effects of androgens on period are a result of hormonal modulation of the SCN's response to photic input rather than to a change in the inherent period of oscillators in the absence of light.

Original languageEnglish (US)
Pages (from-to)2344-2352
Number of pages9
JournalEndocrinology
Volume153
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

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Circadian Clocks
Suprachiasmatic Nucleus
Androgens
Light
Androgen Receptors
Darkness
Circadian Rhythm
Hormones
Dihydrotestosterone
Locomotion
Pupil
Theophylline
Constriction
Running
Cues
Testosterone
Neurons

ASJC Scopus subject areas

  • Endocrinology

Cite this

Dose-dependent effects of androgens on the circadian timing system and its response to light. / Butler, Matthew; Karatsoreos, Ilia N.; Sauter, Joseph Le; Silver, Rae.

In: Endocrinology, Vol. 153, No. 5, 05.2012, p. 2344-2352.

Research output: Contribution to journalArticle

Butler, Matthew ; Karatsoreos, Ilia N. ; Sauter, Joseph Le ; Silver, Rae. / Dose-dependent effects of androgens on the circadian timing system and its response to light. In: Endocrinology. 2012 ; Vol. 153, No. 5. pp. 2344-2352.
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