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Circadian, Ultradian, and Episodic Release of β-Endorphin in Men, and Its Temporal Coupling with Cortisol^*

Endocrine Section, Veterans Administration Medical Center (A.I., G.L.) Salem, Virginia 24153
The Division of Endocrinology and Interdisciplinary Graduate Biophysics Program, Departments of Internal Medicine and Pharmacology, University of Virginia School of Medicine (M.L.J., J.D. V.) Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Ali Iranmanesh, M.D., Veterans Administration Medical Center, Endocrine Section (HIP), Salem, Virginia 24153.

β-Endorphin and ACTH derive from a common peptide precursor. Although much is known about the physiological patterns of ACTH release, neither the minute to minute regulation of β-endorphin secretion nor its temporal relationship to cortisol has been characterized. As an initial step to defining the regulation of β-endorphin release in man, we studied the circadian periodicity, ultradian rhythmicity, and episodic pulsatility of serum j8-endorphin concentrations in seven normal men. Blood sampling was conducted at 10-min intervals for 24 h, and the subsequent serum samples were assayed by a two-site immunoradiometric assay. Computerized analysis of the subsequent β-endorphin time series revealed a mean β-endorphin pulse frequency of 13 ± 1 (±SE) peaks/24 h, corresponding to an interpulse interval of 100 ± 7 min. The mean maximal peak height of β-endorphin pulses was 31 ± 3 pg/mL (9.0 ± 0.8 pmol/L), which represented an incremental increase of 11 ± 1 pg/mL 3.2 ± 0.4 pmol/L; 63 ± 13%) above the preceding nadir. The average β-endorphin peak exhibited a duration of 68 ± 6 min. Fourier analysis revealed a significant circadian amplitude of 6 ± 1 pg/mL (1.6 ± 0.4 pmol/L; 23% of the 24-h mean concentration), with an acrophase (time of maximum value) at 1043 h (± 40 min). Spectral analysis also disclosed β-endorphin rhythms with mean periodicities of 29 ± 4, 42 ± 4, and 61 ± 5 min. Gel filtration chromatography confirmed that serum β-endorphin peaks contained significantly more immunoactive β-endorphin [62 pg/mL (18 pmol/L) ] than did the flanking nadirs [16 and 18 pg/mL (4.6 and 5.2 pmol/L)]. Auto- and cross-correlation analyses of serum β-endorphin and cortisol concentrations followed by autoregressive modeling disclosed that all seven men had significant positive cross-correlations between serum β-endorphin and cortisol considered simultaneously or when cortisol lagged β-endorphin by 10 min. A negative cross-correlation was found in five of the seven men when cortisol was considered to lead β-endorphin by 20 or 30 minutes. We conclude that β-endorphin is released physiologically in a pulsatile manner with circadian and ultradian rhythmicity and a close temporal coupling to cortisol.

^* This work was supported in part by V.A. Medical Research funds (to A.I.), 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-8928 (to M.L.J.), Diabetes and Research Training Center Grant 5-P60-AM-22125-05, and NIH-supported Clinfo Data Reduction Systems.

Received September 6, 1988.

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