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.

Juvenile hormone affects the development and strength of circadian rhythms in young bumble bee (Bombus terrestris) workers

“…This idea is consistent with studies with rodents showing that sex steroids affect various circadian parameters of locomotor activity, including the phase, FRP, amplitude (i.e., strength), and splitting of locomotor activity rhythms (Daan et al, 1975;Morin, 1980;Morin et al, 1977; reviewed in Hatcher et al, 2020). Many of these effects could be attained by acute pharmacological treatments acting on hormone receptors indicating that the hormonal influence is activational rather than developmental (e.g., Karatsoreos et al, 2011;Model et al, 2015). In addition, treatments with steroid hormones were shown to regulate the expression of genes that are important for the generation or expression of circadian rhythms within specific cells, or by enhancing coupling within the timekeeping system (e.g., Karatsoreos et al, 2011;Nakamura et al, 2008Nakamura et al, , 2005reviewed in Hatcher et al, 2020).…”

Neuroendocrine underpinnings of sex differences in circadian timing systems

“…Treatment of gonadectomized males with testosterone reinstates the shorter period typical of the intact animal [55]. Impressively, the change in period does not require extra-SCN brain regions or peripheral effectors as testosterone implants directly in the brain, near the SCN, also produce a shortening of the free-running period in gonadectomized male mice [56]. In addition to modulating SCN timekeeping and locomotor activity, testosterone also modulates SCN responsiveness to light [57].…”

Circadian Insights into Motivated Behavior

“…The major inputs to the SCN arise from the eye, the raphe nuclei in the brain stem, and the intergeniculate leaflet of the thalamus, although numerous other regions also send direct projections to the SCN (Krout et al 2002). Information regarding the internal state of the body, such as those provided by testicular and ovarian hormones, acts directly on hormone receptors within the SCN (Vida et al 2010;Model et al 2015) which are themselves under circadian control. In turn, the SCN sends projections to a number of areas in the brain (Kriegsfeld et al 2004), some of which may serve as nodes to distribute circadian signals widely (Vujovic et al in press) or integrate circadian signals with other homeostatic and sensory signals (Saper et al 2005a).…”