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Operating Characteristics of the Hypothalamo-Pituitary-Gonadal Axis in Men: Circadian, Ultradian, and Pulsatile Release of Prolactin and Its Temporal Coupling With Luteinizing Hormone^*

Department of Internal Medicine, Division of Endocrinology (J.D.V.), and the Department of Pharmacology, Division of Biomathematics (M.L.J.), University of Virginia School of Medicine Charlottesville, Virginia 22908

Address requests for reprints to: Dr. Johannes Veldhuis, Box 202, University of Virginia School of Medicine, Charlottesville, Virginia 22908

To investigate the circadian, ultradian, and pulsatile nature of PRL release in the human, we sampled blood at 10-min intervals for 24 h in each of 12 normal young men. The subsequent serum PRL time series were subjected to contemporary techniques of rhythmic and episodic peak detection. Fourier analysis revealed a significant circadian rhythm in serum PRL concentrations in all 12 men. The mean circadian amplitude was 2.1 ± 0.3 ng/mL (µg/L), which accounted for an average of 30 ± 4% of the 24-h mean PRL concentration. In addition, multiple ultradian PRL rhythms were found with periodicities ranging from 22–242 min. Spectral analysis disclosed ultradian cycles with periodicities of 30–32, 51–59, 90–98, and 234 min. Assessment of episodic PRL pulsatility by Cluster analysis revealed 14 ± 1 PRL peaks/24 h (P < 0.01 vs. signal-free noise), which occurred at an interpulse interval of 95 ± 6 min. The average duration of a serum PRL peak was 67 ± 5 min, and its incremental amplitude was 4.0 ± 0.3 ng/ml (µg/L), which represented a 58 ± 6% increase above the preceding nadir. Discrete PRL peaks were separated by nonpulsatile valleys, with a mean duration of 27 ± 1 min. Analysis of the temporal coupling between LH and PRL release by bivariate autoregressive modeling in six men revealed significant cross-correlations between LH and simultaneous PRL concentrations as well as between LH and PRL concentrations that lagged LH by 10 or 20 min. Cross-spectral analysis demonstrated significantly correlated PRL and LH cycles with periodicities of 33–37, 47–52, and 84–106 min. In summary, PRL release in normal young men characterized by significant circadian and ultradian periodicities, by discrete episodic pulsations that occur approximately every 95 min, and by a close temporal coupling with LH (temporal lag between LH and PRL of 0–20 min).

^* This work was supported in part by NIH Grant RR 00847 to the Clinical Research Center of the University of Virginia, Research Career Development Award 1-K04-HD-00634 (to J.D.V.), NIH Grants AM-30302 and GM-28928 (to M.L.J.), Diabetes and Research Training Center Grant 5-P60-AM-22125-05, and NIH-supported Clinfo Data Reduction Systems.

Received December 7, 1987.

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