Chronobiologic study of neuro-endocrine axis hormone sequence signalling in healthy men

Abstract

The neuro-endocrine system function is characterized by a large number of circadian processes that signal each other in sequence with different rhythm phases over 24 h. The morning peak of cortisol secretion and the nightly peak in melatonin secretion are well-known physiological phenomena. Thyroid-stimulating hormone (TSH) secretion shows higher levels at night, whereas free thyroxine (FT4) levels do not seem to change with circadian rhythmicity. Similarly, growth hormone (GH) is secreted with higher levels at night, but insulin-like growth factor (IGF)-1 production shows only minor fluctuations over 24 h. In order to look for rhythmicity and phasing (acrophase, Ø) in the dynamics of variation over 24 h, we investigated adrenal and pineal gland, pituitary-thyroid axis, and GH-IGF-1 axis secretions of cortisol, melatonin, TSH, FT4, GH and total IGF-1 in serum levels every 4 h for 24 h from 11 healthy men, age: 35–53 years. Circadian rhythmicity was evaluated for original values and for the fractional variation (FV) between single time point values that was calculated to evaluate the percentage change in rise and fall. A 24 h cosine significantly described the circadian waveform for serum levels in cortisol, melatonin, TSH and GH (Ø = 07:48 h, 01:35 h, 23:32 h, 00:00 h, respectively), while a 12 h cosine significantly described two peaks for serum levels in FT4 (Ø = 09:44 h and 21:44 h, P = 0.038), and in IGF-1 (Ø = 07:40 h and 19:40 h, P = 0.013). A 24 h cosine also significantly described the circadian waveform for FV of cortisol (02:00 h), melatonin (22:29 h), FT4 (05:14 h), and GH (21:19 h), while a 12 h cosine significantly described two peaks for FV of TSH (04:28 h for fall and 16:28 h for rise), whereas FV of IGF-1 did not show a rhythmic pattern. Thus, maximal FV estimated by 24 h Øs preceded maximal serum levels by ∼6 h for cortisol and TSH, ∼5 h for FT4, ∼3 h for melatonin, ∼2.5 h for GH, and ∼1 h for IGF-1. When comparing 24 h Øs for serum levels of hormone pairs, the peak for melatonin preceded that for cortisol by 6 h, the peak for TSH preceded the first peak of FT4 by 10.5 h, and the peak for GH preceded that for IGF-1 by 8 h. When comparing FV pairs, the peak for melatonin surge preceded that for cortisol by ∼3.5 h, the peak for TSH surge preceded that for FT4 by ∼13 h, and the peak for GH rise preceded that for IGF-1 ∼10 h. In conclusion, the neuro-endocrine system function is characterized by circadian organization, with individual components showing different phasic patterns of time-related variations, and this array of rhythms undoubtedly underlies the maintenance of stable, but rhythmic and thus predictive, homeostatic processes in the human body.