A report in the November Cell Metabolism reveals powerful effects of light on the adrenal glands, a finding that might explain the broad benefits of bright light therapy for a variety of conditions, including sleep and depressive disorders, according to researchers. The body's two adrenal glands sit atop each kidney, where they secrete hormones that regulate stress response and metabolism.
The researchers found in mice that light sparks a cascade of gene activity in the adrenal gland through its effects on the suprachiasmatic nucleus (SCN). Located in the brain region called the hypothalamus, the SCN is the seat of the circadian clock, the body's internal clock that regulates the roughly 24-hour cycle of biological processes.
Moreover, the researchers report, the gene expression changes accompany a massive surge of the steroid hormone corticosterone in the animals' blood and brain. That hormonal response increased with light intensity, they found.
Glucocorticoids--including cortisone in humans and corticosterone in mice--play many roles throughout the body, including metabolic response to starvation, antiinflammatory immune response, and the timing of circadian rhythms in peripheral organs. Therefore, light-induced secretion of glucocorticoids may play a key role in physiological changes in the body and the brain evoked by light, reported study author Hitoshi Okamura of Kobe University Graduate School of Medicine in Japan
First introduced in the early 1980s for the treatment of seasonal affective disorder, bright light therapy has been applied to many sleep disorders, including jet lag syndrome and shift work sleep disorder, the reseachers said. Shift work sleep disorder, which affects people who frequently rotate shifts or work at night, is often accompanied by metabolic symptoms, including hypertension, cancer, and diabetes.
"In these patients, light therapy improves not only psychiatric status, but also disordered hormones and metabolisms," Okamura said. "However, effects of light had only been established on melatonin, and the remaining powerful and broad effects of light on body metabolism and hormones remained to be clarified."
The researchers examined the activity of the clock gene Per1 in the organs of living animals. The team found that nighttime light exposure induced Per1 expression in the adrenal gland. Further analysis of the gland revealed numerous changes in the activity of almost 200 genes, followed by the delayed release of corticosterone.
When the researchers severed the SCN, light's effect on the gland was lost, indicating that the phenomenon is closely linked to the circadian clock, they said.
"The surge of blood corticosterone after light exposure indicates that environmental signals are instantly converted to glucocorticoid signals in the blood and cerebrospinal fluid," Okamura reported. "The present light-induced corticosterone release may entrain metabolically peripheral clocks to the environmental light-dark cycle through its prevailing receptors located in virtually all cells in the body."
The findings could prove of great clinical and physiological interest, wrote Ueli Schibler and Steven Brown in an accompanying commentary.
"If a light-induced pathway were also operative in humans, a question that could readily be examined by recording blood cortisone levels after light exposure, it would be tempting to speculate that cortisone-mediated synchronization of peripheral circadian clocks would be one of the beneficial effects light therapy has on patients with seasonal affective disorder," Schibler and Brown said.
"It might also explain why bright light therapy can aid patients with other disorders--such as major depressive disorder and bipolar disorder--not typically associated with the circadian clock," they continued.
The researchers include Atsushi Ishida, Tatsushi Mutoh,Tomoko Ueyama,Satoru Masubuchi, and Hitoshi Okamura of the Kobe University Graduate School of Medicine in Kobe, Japan; Hideki Bando of Kobe University Graduate School of Medicine in Kobe and of Kyoto Prefectural University of Medicine in Kyoto, Japan; Daiichiro Nakahara of Hamamatsu University School of Medicine, Hamamatsu, Japan; and Gozoh Tsujimoto of Kyoto University Graduate School of Pharmaceutical Sciences in Kyoto, Japan. This work was supported by Scientific Grants from the Ministryof Health, Welfare, and Labor, The Special Coordination Funds and the Scientific Grants of the 21st Century COE Program from Ministry of Education, Culture, Sports, Science, and Technology of Japan, SRF, and Hyogo Science and Technology Association.
Ishida et al.: "Light activates the adrenal gland: Timing of gene expression and glucocorticoid release." Publishing in Cell Metabolism Volume 2, November 2005, pages 297 - 307. DOI 10.1016/j.cmet.2005.09.009 www.cellmetabolism.org
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