General remarks on endocrine rhythms

The daily hormonal variation was first described in 1943 by Pincus (urinary ketosteroid secretion). In chronobiological research, the studies have been concentrated on the endocrine circadian time structure (ECTS), as it is the easiest to extrapolate and to apply in practice.

In this context some general points should be noted.

The circadian changes in hormones may depend on .each other; even an apparently subordinate rhythm should, however, be considered a true inde­pendent rhythm.

Accurate studies have shown that hormonal secretion occurs in all cases according to a rhyth­mic organization at many levels. However, this rhythm may not be evident at a first analysis, since it has not been proved that all hormones have a circadian rhythm only and they may thus undergo periods of infradian and, particularly, of ultradian rhythm.

What should be underlined is that hormone se­cretion is basically pulsating; the pulsation of hor­mone secretion makes it difficult to draw a standard reference curve and explains the difference in hor­mone levels observed in various subjects examined and in the same subject over the same observation period. The statistical analysis of the rhythmic pattern of hormone secretion eliminates the minor components and clearly evidences the circadian rhythm, with similar peak and nadir values in the different subjects.

Moreover, most of the data obtained in the different research centers regarding the rhythmic oscillation of hormone levels are quite comparable from one subject to another when sampling is fairly frequent and at regular intervals, for example every hour, or fraction of an hour.

Fig. 4 summarizes the circadian pattern of 8 hormones: cortisol, GH, aldosterone, PRL, testo­sterone, TSH, LH and FSH when the sampling is hourly or at every fraction of an hour. The use of intensive and, at the same time, extensive sampling has allowed a more detailed and realistic picture of the range of physiological variation of hormonal secretion. In addition, the application of more analytical techniques (cluster analysis, spectral analysis, etc.) performed simultaneously has re­vealed multiple ultradian rhythms for several hor­mones.

Fig. 4. - Circadian time structure of eight plasma hormones in man. Mean values from a number of studies (P) with sampling occurring at hourly intervals at least.

Although an ECTS is present at the cell level, in organs etc., it is evident that a rhythm hierarchy exists. The circadian rhythmic variation in neuro­transmitter and neuropeptide levels can have a circadian pattern similar to that of nerve cells but, on account of their intrinsic hierarchical role, they promote an oscillatory function which becomes the most important for the whole circadian time struc­ture.

Hormonal secretion and sleep-wake cycle

The relationship between circadian rhythms and the sleep-wake cycle is particularly important in the field of endocrine rhythms. As suggested by Aschoff, “m view of the multi-oscillatory structure of the circadian system, it is of great interest to know whether a variable represents a circadian rhythm in itself or whether its rhythm is a (passi­ve) consequence of another rhythmic variable” [42]. Although several reports state that no rhythm is totally dependent on the sleep-wake cycle, from a general point of view the hormone secretion rhythms can be divided in: 1) sleep-dependent rhythms; 2) sleep-independent rhythms.

Rhythms that seem to be strictly sleep-depend­ent, for example GH and prolactin secretion, ac­tually display a sleep-independent rhythmic com­ponent showing (<a) a basic (minimal) hormone secretion without sleep, (b) a sleep-independent (small amplitude) rhythm of secretory activity and (c) a strong circadian rhythm of responsiveness to sleep [42, 43] (Fig. 5).

Fig. 5. - An experiment which shows the strong corre­lation between the stages of sleep and GH secretion in healthy males administered 250 mg Tolbutamide every 4 hours is represented. It can be noted that in the last part of the night hormone secretion peaks are not documented, even in the presence of REM phases.

Unlike GH, cortisol has been shown to have a strong independent periodic component [43-47].