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While GHSR1a constitutive activity is required for amplification of MC3R signaling, it has minimal effect on GHSR1a-MC3R dimer internalization, as treatment with the GHSR1a inverse agonist SP-analog only results in a small, nonsignificant reduction in internalization (Schellekens et al., 2013)

Morning cortisol peaks (the cortisol awakening response) occur between 69 AM in most people

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These changes seem small on paper