Circadian Rhythm Research Standard: Melatonin Scientific Profile

Introduction

This document outlines the scientific profile of melatonin, the core biomarker used in chronobiological research. Melatonin serves as the primary standard for investigating the human and animal circadian system, offering critical insight into the timing and function of the body's master clock.

Scientific Profile

Melatonin is recognized as the primary biomarker for chronobiological research due to its tight synchronization with the light/dark cycle and its role in regulating the timing of biological processes.

Mechanism of Action

Melatonin exerts its effects by acting on specific G-protein coupled receptors.

Receptor Type

Location

Function

MT1

Suprachiasmatic Nucleus (SCN), Pars Tuberalis

Inhibits neuronal firing in the SCN, promoting sleep

MT2

SCN, Retina

Involved in phase-shifting effects and photoperiodic regulation

The suprachiasmatic nucleus (SCN), located in the hypothalamus, is often referred to as the body's master clock. Melatonin signals directly to the SCN to synchronize the internal body time with the external light/dark cycle.

Regulation by the Light/Dark Cycle

Melatonin secretion is tightly regulated by photoperiod (light exposure), providing a precise signal of "biological night."

• Darkness: Secretion begins shortly after the onset of biological night, often referred to as Dim Light Melatonin Onset (DLMO), and peaks during the middle of the dark phase.
• Light: Exposure to light, particularly blue-wavelength light, rapidly suppresses melatonin production, signaling biological day.

[A graph showing plasma melatonin levels in a wavy line over a 24-hour period, with low levels during the light period and high levels peaking during the dark period]

Role in Phase Shifting

A critical function of melatonin in research is its capability to phase shift the circadian rhythm.

Application

Description

Research Focus

Jet Lag

Administered to help models rapidly adjust the timing of their internal clock (phase advance or delay) to a new time zone.

Resynchronization and reducing symptoms.

Shift Work

Used in simulations to manage and mitigate the negative health consequences of chronic circadian misalignment.

Timing and dose required to shift the clock.

The relationship between the timing of exogenous melatonin administration and the resulting shift in the circadian clock is mapped out in the Melatonin Phase Response Curve (PRC), a fundamental tool in chronobiology.

Ideal Applications

This standard is ideal for research focused on:

• Sleep Latency Assays: Measuring the time required to fall asleep after introduction of the reagent.
• Chronobiology Studies: Investigating human and animal timing systems, including the influence of genetic polymorphisms.
• Pineal Gland Function Research: Assessing the endogenous output capacity of the pineal gland, where melatonin is synthesized.

Status

Experimental Reagent.

This product is intended for research use only and is not for human or therapeutic use.

Related Research Methods and Considerations

To effectively use the Circadian Rhythm Research Standard, researchers must employ rigorous sample collection and analytical techniques.

Sample Collection and Timing

The accurate determination of the circadian phase requires repeated sample collection throughout a controlled 24-hour period, typically under constant routine (CR) or dim light conditions to minimize external masking effects.

Sample Type

Collection Method

Notes

Saliva

Passive drool or cotton swab collection

Non-invasive; reflects free, active fraction of melatonin.

Plasma

Venipuncture

Invasive; measures total plasma melatonin concentration.

Urine

Timed collection

Used to measure the primary metabolite, 6-sulfatoxymelatonin (aMT6s).

Optimal timing for phase assessment is the Dim Light Melatonin Onset (DLMO), which is defined as the time when melatonin concentration exceeds a predefined threshold (typically 2-4 pg/mL) under strictly controlled, dim light conditions (<30 lux).

Assay Validation

All analytical methods, such as radioimmunoassay (RIA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), must be rigorously validated for the chosen sample matrix, ensuring high sensitivity and specificity, particularly at the low physiological concentrations found at the DLMO.

Research Compliance and Ethical Guidelines

All studies involving the use of this research standard and human subjects must adhere to the following:

1. Institutional Review Board (IRB) Approval: All protocols must be reviewed and approved by the corresponding institutional ethics committee.
2. Informed Consent: Subjects must provide written informed consent detailing the purpose, risks, and procedures of the chronobiological study.
3. Light Control: Strict control over ambient light exposure is necessary to prevent acute melatonin suppression, ensuring the integrity of the collected data. This typically involves maintaining light levels below 10 lux during the critical sampling periods.

Researchers are advised to consult the latest guidelines for chronobiological research provided in Standardization in Human Chronobiology: Consensus Recommendations File.

Future Directions in Melatonin Research

Current research is exploring the broader systemic effects of melatonin beyond the SCN, including its role as a potent antioxidant and its potential involvement in metabolic health.

Systemic Role

Research Area

Expected Outcome

Antioxidant

Neuroprotection in degenerative diseases

Development of new therapeutic delivery methods.

Metabolic

Glucose homeostasis and insulin sensitivity

Understanding the link between circadian disruption and Type 2 Diabetes.

Immune

Regulation of inflammatory responses

Clarification of melatonin's role in immune synchronization.

Further studies are needed to understand the chronic effects of phase shifting and the individual variability in response to exogenous melatonin administration. This variability may be attributed to genetic differences in melatonin receptor expression or metabolism. Researchers are encouraged to report any unique findings to the research community by sending an email to Person@research.edu.

We plan to hold a virtual workshop on advanced melatonin phase assessment techniques. Details for joining the workshop can be found here: Calendar event.

Ordering and Technical Support

For inquiries regarding batch availability, Certificate of Analysis (CoA), and technical specifications, please contact our research support team.

• Technical Support: Person
• Email: support@circadianresearch.com
• Phone: 1-800-MELATONIN

The Circadian Rhythm Research Standard is manufactured and shipped from our certified laboratory located in Place. All orders placed by Date will ship the following business day.

This document serves as a foundational guide for the Melatonin Research Standard. For ongoing updates and new technical bulletins, please monitor the official product page.