抄録
Circadian rhythms are generated by a cell-autonomous circadian oscillator that is synchronized with the daily 24-h light-dark (LD) cycle. The mammalian master circadian oscillator is located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Period (Per) genes play important roles in a core molecular clock involving self-sustained transcriptional positive and negative feedback loops underlies circadian rhythmicity in cells and tissues. Gonadal steroid hormones, especially estrogen (E), appear to shorten the free-running period (τ) of the locomotor activity rhythm in rodents. We investigated the mechanism by which steroid hormones influence rhythms, relying on a combination of locomotor activity recording and clock gene expression analysis in Period1-luciferase (Per1-luc) transgenic rats. Treatment with gonadal steroid hormones in the physiological range (200nM-1μM) did not affect rhythms of Per1-luc expression in SCN tissue explants from transgenic Per1-luc rats. However, at higher concentrations (10μM-500μM), steroid hormones (E, P, E+P) reduced the amplitude of Per1 expression while progesterone (P) alone increased the τ of Per1 expression. Chronic treatments with E, P and E+P reduced the τ of running wheel activity. These findings suggest that changes in behavior induced by steroid hormones require a neural circuit, including the primary circadian clock in the SCN, and a steroid responsive region of the brain that interacts with the SCN and may be located within the hypothalamus. [J Physiol Sci. 2007;57 Suppl:S63]
