Characteristics of pulsatile and circadian prolactin release and its variability in men^*

Summary

In order to investigate the intra- and interin-dividual variability of spontaneous prolactin (PRL) secretion, 24 h blood sampling at 10 min intervals was performed in ten healthy young men (age 19 to 25 yrs) on three occasions (intervals 2 weeks and 3 months). Plasma PRL concentrations were determined in duplicate by immunoradiometric assay. Peak detection was carried out with the PULSAR program. The circadian rhythm was analyzed by a complex cosinor method combining fundamental (24 h), 1st harmonic (12 h), and 2nd harmonic (6 h) frequencies. The original data was well represented by this calculation as shown by mean (± SD) correlation coefficients of 0.84 ± 0.08. Mean and integrated PRL concentrations showed the lowest intraindividual variability (range 2.8 to 19.6%) of all parameters tested. For the number of peaks per 24 h, a median intraindividual variability of 24.2% (range 6.9 to 50%) was seen. In general, intraindividual variability of parameters of pulsatile PRL release was lower than the variability between subjects.

The complex cosinor analysis revealed a bimodal pattern of PRL secretion in most profiles. Acrophases (times of highest PRL levels) were found between 0040 and 1000 h, nadirs between 0030 and 2300 h. The amplitude of the circadian rhythm (Max-Min) ranged from 3.8 to 16.9 ng/ml. The time lag between onset of sleep and acrophase was variable (1.75 to 7.83 hrs). Variability of nadir, minimal and maximal PRL, amplitude, and minimal PRL as percent of the mesor was significantly lower within individuals than between subjects (p < 0.02).

During sleep, peak heights and peak amplitudes were significantly higher than during waking periods (p < 0.004). No statistically significant differences were found in the distribution of relative frequencies of peak number, peak amplitudes and peak heights between the three series of profiles. The distribution of peak heights was compatible with a normal distribution.

In conclusion, it was shown that the circadian rhythm of PRL secretion in normal men can be analysed accurately and reliably with the complex cosinor method, which is relatively easy to perform and yields results comparable to those obtained by much more complicated programs. Spontaneous PRL secretion in healthy young men is characterized by pulsatile secretion (in all profiles) and by circadian rhythmicity (in all profiles), with the majority of profiles showing a bimodal pattern. The day-night differences appear to be an amplitude-modulated phenomenon. The stable distribution of peak heights, amplitudes, and duration provides evidence for a rather fixed pattern of PRL secretion, similar to that of GH and LH. For most parameters of pulsatile and circadian PRL secretion, intraindividual variability (medians 7 to 30%) is lower than the variation between individuals (16 to 54%). This variability has to be taken into account when analysing or interpreting results from therapeutic or pathophysiologic studies.

Key words

Prolactin - pulsatile secretion - circadian rhythm - chronobiology