Is Vitamin D Signaling Regulated by and Does It Regulate Circadian Rhythms?

Area of Science:

• Chronobiology
• Endocrinology
• Molecular Biology

Background:

• Recent findings suggest vitamin D3 (D3) impacts sleep behavior.
• The interplay between D3 metabolism and the circadian system is not fully understood.

Purpose of the Study:

• To investigate if the circadian clock regulates D3 activation.
• To determine if active D3 forms modulate molecular clock elements.

Main Methods:

• Review of experimental and molecular evidence.
• Analysis of molecular modeling data.
• Literature review on D3 metabolites and circadian regulation.

Main Results:

• Circadian regulation of D3 production (25(OH)D3 and 1,25(OH)2D3) is not supported.
• Evidence suggests the circadian network may influence CYP11A1 activity and D3-hydroxyderivative production.
• D3-hydroxyderivatives interact with RORs and REV-ERBs, known regulators of clock genes.

Conclusions:

• D3-hydroxyderivatives may directly regulate circadian clock genes via RORs and REV-ERBs.
• D3-hydroxyderivatives might indirectly affect the circadian clock through melatonin.
• Vitamin D3 signaling is proposed to be regulated by the circadian network and to directly modulate the molecular clock.