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I I I I I I I I I I I I I I I I I Life Sciences, Vol. 28, pp. 1637 -1640 PerRamon Press Printed in the U.S.A. THE EFFECT OF RUNNING ON PLASM.4 8-ENDORPHIN Edward W. D. Colt, Sharon L. Wardlaw, and Andrew G. Frantz Departments of Medicine, St. Luke's-Roosevelt Hospital Center and Cclumbia University College of Physicians and Surgeons (Received in final form January 30, 1981) Summary Plasma 8-endorphin immunoactivity was measured by RIA in 26 trained long distance runners on 35 occasions before and after running. Mean total B-endorphin immunoactivity in- creased from 11.8 + 1.8 (SEM) to 17.6 + 3.1 pg/ml in 20 runners after an easy run (p = .067), and from 8.2 + 1.03 to 28.0 + 6.3 pg/ml in 15 runners after a strenuous run (p = .008). Total 8-endorphin immunoactivity in the plasma extracts of 7 runners before and after the strenuous run was further characterized by•Sephadex G-50 chromatography in order to separate 8-endorphin from corssreacting 8-lipotropin (B-LPH). A rise in B-endorphin and 8-LPH concentrations after running was noted in 5 out of 7 runners. Physical exercise stimulates the secretion of several anterior pituitary hormones. Running and bicycling have been shown to increase plasma prolactin and growth hormone levels (1,2). Bicycling and treadmill exercise have been reported to increase plasma cortisd presumably by the stimulation of ACTH release, although the effect of exercise on plasma ACTH concentration in man has not been well documented (2,3). Both ACTH and B-endorphin (the C-ter- minal end of 8-lipotropin) are synthesized in the pituitary from a common 31,000 MW precursor and are secreted in man in response to known ACTH- releasing stimuli such as metyrapone and hypoglycemia (4-6). We have pre- viously reported in the rat that ACTH and B-endorphin are secreted in paral- lel into the peripheral blood in response to swimming (7) . In this study we report that running increases plasma 6-endorphin levels in trained long dis- tance runners. Materials and Methods Subjects. 26 trained long distance runners (6 females and 20 males) volunteered for the study on a total of 35 occasions. For this study a runner was defined as a male who regularly ran a minimum of 48 km per week or a female who regularly ran a minimum of 24 km per week for 3 months prior to the test runs. Twenty runners participated in the first test run which was 6.4 to 12.8 km in length. All runners started at 8:00 to 8:30 A.M. and ran at a self- regulated comfortable speed. Nine of the original runners and six additional runners also participated in a second run which differed from the first run only in that the effort was close to maximal. Blood samples were collected on ice in heparinized tubes immediately prior to and after the test runs. Plasma was frozen at -20 C and stored for 1 to 6 weeks before radioimmunoassay. Extraction, Chromatography, and RIA 5 ml plasma samples were extracted with talc and assayed for total B-en- 0024-3205/81/141637-04S02.00/0 Copyright (c) 1981 Pergamon Press Ltd. I

I I I I I I I I I I I I I I 1638 Effect of Running on Plasma i-Endorphin Vol. 28, No. '-'~, :981 dorphin immunoactivit,v by RIA essentially as reported previously (4,8). RIA was performed with an antiserum to human 8-endorphin which corssreacts 10.8% on a weight basis with human B-LPH, and synthetic human S-endorphin standard (Peninsula Laboratories, Inc., San Carlos, CA). Current assay sensitivity is 10 pg of B-endorphin per tube. In seven cases 20 ml plasma samples were extracted and the extracts chromatographed on Sephadex (-50 columns (0.9 x 50 cm) in 0.1ti acetic acid plus 0.2% bovine serum albumin in order to separate B-endorphin from corssreacting B-LPH. 8-LPH concentra- tions were calculated by dividing the immunoactivity eluting under the S-LPH peak by 0.108 in order to correct for the 10.8% crossreactivity of the anti- serum wit}• B-LPH as compared to 8-endorphin. Human B-LPH was kindly supplied by Dr. C.H. Li. Recovery of 5-endorphin and B-LPH from plasma averaged 75% after extraction, and 68% after extraction and chromatography. All plasma concentrations of 8-endorphin and 8-LPH were corrected for recovery. Results Mean total S-endorphin immunoactivity increased from 11.8 + 1.8 (SEM) to 17.6 + 3.1 pg/ml in the 20 runners after the initial easy run (p =.067). An increase was noted in 9 out of 20 runners as shown in Table 1. After the strenuous run 12 out of 15 runners exhibited a rise in plasma B-endorphin immunoactivity (Table 1). Mean 8-endorphin immunoactivity increased from 8.2 + 1.03 to 28.0 + 6.3 pg/ml after the strenuous run (p = .008). Of the 4 runners that exhibited a rise in S-endorphin immunoactivity during the easy run and subsequently ran the strenuous run, all showed an increase in 8-endor- phin immunoactivity the second time. A negative correlation (R= -0.5143, p< .05) was noted between the per- cent change in B-endorphin over the baseline and the years of training in the IS runners who participated in the strenuous run. Total S-endorphin immunoactivity in the plasma extracts of 7 runners before and after the strenuo:a run was further characterized by Sephadex G-50 chromatography in order to measure B-endorphin and B-LPH separately. The 8-endorphin and B-LPH concentrations and 8-endorphin/B-LPH molar ratios are shown in Table 2. A rise in B-endorphin and B-LPH concentrations was noted in 5 out of 7 runners. Discussion Our finding that running stimulates the secretion of B-endorphin and B-LPH is consistent with previous reports that bicycling and treadmill exercise are associated with increases in plasma cortisol presumably mediated by in- creased ACTH secretion (2,3). Thus physical exercise appears to stimulate the release of s-endorphin, 8-LPH, and ACTH, all three of which are synthe- sized together in the pituitary from a conunon precursor. The stimulation of B-endorphin by running appears to be related to the effort intensity of the runners. After the first easy run a rise in S-endorphin was noted in only 4S% of runners, but after the strenuous run S-endorphin increased in 80% of the runners. The percent increase in S-endorphin over baseline correlated negatively with the number of years the runners had been training. Hartley and colleagues have reported similar rises in plasma cortisol after bicycling in young males before and after a seven week training period. The effect of more prolonged training was not studied.(2)• ~ ~ ~ ~ C3:1

I I I I I I I I I I I I I I I I I I Vol. 28, No. 14, 1981 Effect of Running on Plasma 6-Endorphin 1639 TABLE I Effects of Easy and Strenuous Runs on Total Plasma 8-Endorphin Immunoactivity Easy Run Strenuous Run Years B-EP pg/mi 8-EF pg/ml Runners* Age Sex Training Before After Before After BR 27 M 0.25 15 8 MC 29 F 0.25 <7 10 WJ 37 M 0.5 <7 <7 10 17 CR 41 M 0.5 <7 50 GD 29 M 1.5 <7 51 8 86 SG 29 F 1.6 <3.3 6.7 YR 29 M 2 <7 <7 MN 30 M 2 8 18 <4.1 31 LK 33 M 2 8 29 <7 13 BL 36 F 2 20 30 17 33 MJ 41 F 2.1 <7 20 KG 33 M 2.2 _ _ 9.3 68.9 LL 24 F 2.5 21 23 MJ 39 M 2.5 <7 40 GD 28 F 3 <7 <7 CR 36 M 4 <7 <7 <4.2 7.9 SM 39 M 5 <7 <7 HJ 40 M 6.5 15 40 CE 43 M 8 <7 <7 <7 <7 FP 27 M 10 22 42 _ _ RF 42 M 11 <7 13 CR 29 M 12 10.6 9.3 _ _ HE 37 N 12 9.3 <7 15 27 BJ 31 M 13 _ _ 12.2 9.4 MJ 32 M 16 37 23 _ _ SA 33 M 16 <7 <7 4.5 3.4 'Initials coded Although B-endorphin administered centrally has been shown to produce profound behavioral and analgesic effects, it has been reported in man by Foley and colleagues that even large doses of S-endorphin injected peri- pherally are incapable of eliciting these central effects (9). Recently it has been reported that the injection of large amounts of 8-endorphin intravenously may produce behavioral effects in psychiatric patients (10,11). Although these studies suggest the possibility that peripheral 8-endorphin may have central effects, the levels of plasma 8-endorphin achieved in the psychiatric patients were 1000 to 10,000 times higher than the levels we

I I I I I I I I I 1 I I 1 I I I I I 1640 Effect of Running on Plasma =-Endorphin Vol. 28, No. 1~, 1981 TABLE 2 Plasma 8-Endorphin (8-EP) and 8-LPH Concentrations Before and After Running Pre - Run Post - Run 8-EP 8-LPH 8-EP/B-LPH 8-EP 8-LPH 8-EP/8-LPH Runner pg/ml pg/ml molar ratio pg/mi Pg/m_1 molar ratio KG 2.0 86.2 .06 18.4 468 0.11 SA 2.3 20.4 0.31 3.4 <20 - CR <2.1 <19.4 - 5.1 25.6 0.54 MN <2.0 <18.9 - 9.9 193 0.14 BL 7.5 86 0.26 19.3 214 0.27 BJ <2.0 113 - 3.2 57 0.15 SG <1.7 <15.5 - <1.8 61.6 - found after running. Thus we do not believe the decrease in anxiety which has been reported after running (12,13), or other mood changes such as the "runner's high", can be attributed to the small changes which occurred in peripheral plasma 8-endorphin concentrations. Acknowledgement Supported by Grants 5R01-CA-117041 and 5T32-AM-07271 References 1. G.L. NOEL, H.K. SUH, G. STONE, and A.G. FRANTZ, J. Clin. Endocrinol, Metab. 35 840-851 (1972). 2. L.H. HARTLEY, J.W. MASON, R.P. HOGAN, L.G. JONES, T.A. KOTCHEN, E.H. MOUGEY, F.E. WHERRY, L.I. PENNINGTON, and P.T. RICKETTS, J. Appl. Physiol. 33 607-610 (1972). 3. C.T.M. DAVIES, and J.D. FEW, J. Appl. Physiol. 35 887-891 (1973). 4. S.L. WARDLAW, and A.G. FRANTZ, J. Clin. Endocrinol. Metab. 48 176-180 (1979). 5. K. NAKAO, Y. NAKAI, S. OKI, K. HORII, and H. IMURA, J. Clin. Invest. 62 1395-1398 (1978). 6. K. NAKAO, Y. NAKAI, H. JINGAMI, S. OKI, J. FUKATA, and H. IMURA, J. Clin. Endocrinol. Metab. 49 838-841 (1979). 7. S.L. WARDLAW, and A.G. FRANTZ, Clin. Res. 28 482A (1980), 8. R.S. GOLAND, S.L. WARDLAW, R.I. STARK, and A.G. FRANTZ, J. Clin. Endocrinol. Metab. 52 74-78 (1981). 9. K.M. FOLEY, I.A. KOURIDES, C.E. INTURRISI, R.F. KAIKO, C.G. ZAROULIS, J.B. POSNER, R.W. HOUDE, and C.H. LI, Proc. Natl. Acad. Sci. USA 76 5377-5381(1979). 10. P.A. BERGER, S.J. WATSON, H. AKIL, G.R. ELLIOTT, R.T. RUBIN, A. PFEFFERBAUM, K.L. DAVIS, J.D. BARCHAS, and C.H. LI, Arch. Gen. Psychiat. 37 635-640 (1980). 11. R.H. GERNER, D.H. CATLIN, D.A. GORELICK, K.K. HUI, and C.H. LI, Arch. Gen Psychiat. 37 642-647 (1980). 12. R.A. DIENSTBIER, J. CRABBE, G.O. JOHNSON, W. THORLAND, J.A. JORGENSEN, M. M. SADAR, and D.C. LA VELLE, Psychophysiology of Running, M. Sachs and M. Sacks (eds.), Human Kinetics Press, Champaign, 111. (1980). 13. W.P. MORGEN, Psychiat. Ann. 9 36-45 (1979). I