Adrenal peripheral clock controls the autonomous circadian rhythm of glucocorticoid by causing rhythmic steroid production

• DOI: 10.1073/pnas.0806962106
• Publication Date: 2008-12-18T01:55:58Z
• Authors: Gi Hoon Son; Sooyoung Chung; Han Kyoung Choe; Hee-Dae Kim; Sun-Mee Baik; Hankyu Lee; Han-Woong Lee; Sukwoo Choi; Woong Sun; Hyun Kim; Sehyung Cho; Kun Ho Lee; Kyungjin Kim
• Keywords: Male; Hypothalamo-Hypophyseal System; 0303 health sciences; Behavior, Animal; ARNTL Transcription Factors; Nuclear Proteins; Pituitary-Adrenal System; Cell Cycle Proteins; Mice, Transgenic; Period Circadian Proteins; Cell Line; Circadian Rhythm; 3. Good health; Mice; 03 medical and health sciences; Gene Knockdown Techniques; Adrenal Glands; Basic Helix-Loop-Helix Transcription Factors; Animals; Suprachiasmatic Nucleus; Eye Proteins; Glucocorticoids; Transcription Factors

Glucocorticoid (GC) is an adrenal steroid with diverse physiological effects. It undergoes a robust daily oscillation, which has been thought to be driven by the master circadian clock in the suprachiasmatic nucleus of the hypothalamus via the hypothalamus–pituitary–adrenal axis. However, we show that the adrenal gland has its own clock and that the peripheral clockwork is tightly linked to steroidogenesis by the steroidogenic acute regulatory protein. Examination of mice with adrenal-specific knockdown of the canonical clock protein BMAL1 reveals that the adrenal clock machinery is required for circadian GC production. Furthermore, behavioral rhythmicity is drastically affected in these animals, together with altered expression of Period1 , but not Period2, in several peripheral organs. We conclude that the adrenal peripheral clock plays an essential role in harmonizing the mammalian circadian timing system by generating a robust circadian GC rhythm.