Adrenal peripheral clock controls the autonomous circadian rhythm of glucocorticoid by causing rhythmic steroid production.
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.
Son
Gi Hoon
GH
Department of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Chung
Sooyoung
S
Choe
Han Kyoung
HK
Kim
Hee-Dae
HD
Baik
Sun-Mee
SM
Lee
Hankyu
H
Lee
Han-Woong
HW
Choi
Sukwoo
S
Sun
Woong
W
Kim
Hyun
H
Cho
Sehyung
S
Lee
Kun Ho
KH
Kim
Kyungjin
K
D056930:ARNTL Transcription Factors; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000096:biosynthesis* / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D056950:Period Circadian Proteins; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D005136:Eye Proteins; D005938:Glucocorticoids; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse