The endogenous opioids seem likely to be assigned a significant role in the integrated hormonal and metabolic response to exercise. This article reviews the present evidence on exercise and the endogenous opioids, and examines their involvement in a number of widely disparate physiological processes. In considering the role of individual opioid peptides, it is important to remember that many of the tools and techniques now used are still relatively crude.
Most studies have demonstrated that serum concentrations of endogenous opioids, in particular β-endorphin and β-lipotrophin, increase in response to both acute exercise and training programmes. Elevated serum β-endorphin concentrations induced by exercise have been linked to several psychological and physiological changes, including mood state changes and “exercise-induced euphoria”, altered pain perception, menstrual disturbances in female athletes, and the stress responses of numerous hormones (growth hormone, ACTH, prolactin, catecholamines and Cortisol). Many reports have described a role for the endorphin response as seen during exercise and have used the opioid receptor antagonist, naloxone, to investigate and verify the degree of involvement of the opioids. However, whether the observed increases in peripheral endorphin concentrations are sufficient to cause immediate mood changes, create menstrual cycle dysfunction or alter pain perception is still not resolved.
A relatively new implication for the endorphins and associated changes with exercise is in ventilatory regulation. A number of studies have suggested that endogenous opioids depress ventilation and may, therefore, play a role in ventilatory regulation by carbon dioxide, hypoxia and exercise. It may also be possible that during exercise, the perception of fatigue is modulated by an increase of endogenous opioids.
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Akil, H.; Watson, S.J.; Berger, P.A. and Barchas, J.D.: Endorphins, β-LPH, and ACTH: Biochemical, pharmacological and anatomical studies. Advances in Biochemistry and Psycho-pharmacology 18: 125–139(1978).
Ayres, J.; Rees, J.; Lee, T. and Cochrane, CM.: Intravenous naloxone in acute respiratory failure. British Medical Journal 284: 927–928 (1982).
Bahrke, M.S. and Morgan, W.P.: Anxiety reduction following exercise and meditation. Cognitive Therapy Research 2: 323–333(1978).
Baker, E.R.: Menstrual dysfunction and hormonal status in athletic women: A review. Fertility and Sterility 36: 691–696 (1981).
Baker, E.R.; Mathur, R.S.; Kirk, R.F. and Williamson, H.O.: Female runners and secondary amenorrhea: Correlation with age, parity, mileage, and plasma hormonal and sex-hormonal binding globulin concentrations. Fertility and Sterility 36: 183–187(1981).
Barta, A. and Yashpal, K.: Regional redistribution of β-EP in rat brain: The effect of stress. Progress in Neuro-Psychophar-macology 5: 595–598 (1981).
Berk, L.S.; Tan, S.A.; Anderson, C.L. and Reiss, G.: β-EP response to exercise in athletes and non-athletes. Medicine and Science in Sports and Exercise 13: 134 (1981).
Blankstein, J.; Reyes, F.I.; Winter, J.S.D. and Faiman, C: Effects of naloxone upon prolactin and Cortisol in normal women. Proceedings of the Society for Experimental Biology and Medicine 164: 363–365(1980).
Blankstein, J.; Reyes, F.I.; Winter, J.S.D. and Faiman, C: Endorphins and the regulation of the human menstrual cycle. Clinical Endocrinology (Oxford) 14: 287–294 (1981).
Bonen, A.; Belcastro, A.N.; Ling, W.Y. and Simpson, A.A.: Profiles of selected hormones during the menstrual cycle of teenage athletes. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 50: 545–551 (1981).
Bonen, A.; Ling, W.Y.; Maclntyre, K.P.; Neil, R.; McGrail, J.C. and Belcastro, A.N.; Effects of exercise on the serum concentrations of FSH, LH, P and E2. European Journal of Applied Physiology 42: 15–23 (1979).
Bortz. W.M. II; Angevin, P.; Mefford, I.N.; Boarder, M.B.; Noyce, N. and Barchas, J.D.: Catecholamines, dopamine and endorphin levels during extreme exercise. New England Journal of Medicine 305: 466–467 (1981).
Brands, B.; Thornhill, J.B.; Hirst, M. and Gowdey, C.W.: Suppression of food intake and body weight gain by naloxone in rats. Life Sciences 24: 1773–1778 (1979).
Bullen. B.A.; Skrinar, G.S.; Carr, D.B.; Gervino, E.V.; Reppert, S.U.; Dotson, C.O.; Beitins, I.Z. and McArthur, J.W.: Moderate endurance training effects on hormonal responses to serial exercise testing. Journal of Applied Physiology: Respiratory, Exercise and Environmental Physiology. In press (1984).
Carr, D.B.; Bullen, B.A.; Skrinar, G.S.; Arnold, M.A.; Rosenblatt, M.; Beitins, I.Z.; Martin, J.B. and McArthur, J.W.: Physical conditioning facilitates the exercise-induced secretion of β-endorphin and β-lipotropin in women. New England Journal of Medicine 305: 560–563(1981).
Cohen, J.L.; Kim, C.S.; May Jr, P.B. and Ertel, N.H.: Exercise, body weight and amenorrhea in professional ballet dancers. Physician and Sportsmedicine 10: 92–101 (1982).
Colt, E.W.D.; Wardlaw, S.L. and Frantz, A.G.: The effect of running on plasma β-endorphin. Life Sciences 28: 1637–1640 (1981).
Dale, E.; Gerlach, D.H. and Wilhite, A.L.: Menstrual dysfunction in distance runners. Obstetrics and Gynecology 54: 47–53 (1979).
Delitala, G.; Grossman, A. and Besser, G.M.: The modulation of opiate-induced changes in anterior pituitary function by a dopamine agonist and antagonist. Neuroendocrinology Letters 3: 147–152 (1981a).
Delitala, G.; Grossman, A. and Besser, G.M.: Changes in pituitary hormone levels induced by met-enkephalin in man — the role of dopamine. Life Sciences 29: 1537–1544 (1981b).
del Pozo, E.; von Graffenried, B.; Brownell, J.; Derrer, F. and Marbach, P.: Endocrine effect of a methionine-enkephalin derivative (FK-33-824) in man. Hormonal Research 13: 90–97 (1980).
de Weid, D.; Bohus, B.; van Ree, J.M. and Urban, I.: Behavioral and electrophysiological effects of peptides related to lipotropin. Journal of Pharmacology and Experimental Therapy 204: 570–580(1978).
Faiman, C.; Blankstein, J.; Reyes, F.I. and Winter, J.S.D.: Endorphins and the regulation of the human menstrual cycle. Fertility and Sterility 36: 267–268 (1981).
Farrell, P.A.; Gates, W.K.; Morgan, W.P. and Maksud, M.G.: Increases in plasma β-EP and β-LPH immunoreactivity after treadmill running in humans. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 52: 1245–1249(1982).
Farrell, P.A.; Gates, W.K.; Morgan, W.P. and Pent, C.B.: Plasma leucine enkephalin-like radioreceptor activity and tension-anxiety before and after competitive running; in Knuttgen, H.G.; Vogel, J. A. and Poortmans, J. (Eds) Biochemistry of Exercise (Human Kinetics Publishers, Champaign, Illinois 1983).
Fears, W.B.; Yu, J.; Ferguson, E.; Glass, A.R. and Vigersky, R.: Mechanism of exercise-induced secondary amenorrhea. Proc. 65th mtg Endocrine Society, p.86 (1982).
Feldman, M.; Kiser, R.S.; Unger, R.H. and Li, C.H.: β-EP and the endocrine pancreas: Studies in healthy and diabetic human beings. New England Journal of Medicine 308: 349–353 (1983).
Foley, K.M.; Kourides, I.A.; Inturrisi, C.E.; Kaiko, R.F.; Zaroulis, C.G.; Posner. J.B.: Houde, R.W. and Li, C.H.: β-Endorphin: Analgesic and hormonal effects in humans. Proceedings of the National Academy of Science of the U.S.A. 76: 5377–5381 (1979).
Fraioli, F; Moretti, C; Paolucci, D.; Alicicco, E.; Crescenzi, F. and Fortunio, G.: Physical exercise stimulates marked concomitant release of β-endorphin and ACTH in peripheral blood in man. Experientia 36: 987–989 (1980).
Frenk, H.; McCarty, B.L. and Lieberkind, J.C.: Different brain areas mediate the analgesic and epileptic properties of enkephalin. Science 200: 335–337 (1978).
Frisch, R.E.; Wyshak, G. and Vincent, L.: Delayed menarche and amenorrhea in ballet dancers. New England Journal of Medicine 303: 17–19(1980).
Gambert, S.R.; Garthwaite, T.L.; Pontzer, C.H.; Cook, E.E.; Tris-tani, F.E.; Duthie, E.H.; Martinson, D.R.; Hagen, T.C. and McCarty, D.J.: Running elevates plasma β-endorphin immunoreactivity and ACTH in untrained human subjects. Proceedings of the Society of Experimental Biology and Medicine 168: 1–4 (1981a).
Gambert, S.R.; Hagen, T.C; Garthwaite, T.L.; Duthie Jr, E.H. and McCarty, D.J.: Exercise and the endogenous opioids. New England Journal of Medicine 305: 1590–1592 (1981b).
Goldstein, A.; Tachibana, S.; Lowney, L.I.; Hunkapiller, M. and Hood, L.: Dynorphin-(l–13), an extraordinarily potent opioid peptide. Proceedings of the National Academy of Science of the U.S.A. 76: 6666–6670 (1979).
Grevert. P. and Goldstein, A.: Effects of NAL on experimentally induced ischemic pain and on mood in human subjects. Proceedings of the National Academy of Science of the U.S.A. 74: 1291–1294(1977).
Grossman, A. and Besser, G.M.: Opiates control ACTH through a noradrenergic mechanism. Clinical Endocrinology (Oxford) 17: 287–290(1982).
Grossman, A.; Bouloux, P.; Price, P.; Drury, P.; Lam, K.; Alberti, K.; Turner, T.; Besser, G.M. and Sutton, J.R.: The role of opioid peptides in the hormonal responses to acute exercise in man. Clinical Science. (In press, 1984).
Grossman, A.; Gaillard, R.C.; McCartney, P.; Rees, L.H. and Besser, G.M.: Opiate modulation of the pituitary-adrenal axis: Effects of stress and circadian rhythm. Clinical Endocrinology (Oxford) 17: 279–286 (1982a).
Grossman, A.; Moult, P.J.A.; McIntyre, H.; Evans, J.; Silverstone, T.; Rees, L.H. and Besser, G.M.: Opiate mediation of amenorrhea in hyperprolactinaemia and in weight-loss related amenorrhea. Clinical Endocrinology (Oxford) 17: 379–388 (1982b).
Grossman, A. and Rees, L.H.: The neuroendocrinology of opioid peptides. British Medical Bulletin 39: 83–88 (1983).
Guillcmin, R.: Biochemical and physiological correlates of hypothalamic peptides. The new endocrinology of the neuron; in Reichlin, Baldessarini and Martin (Eds) The Hypothalamus, pp. 155–194 (Raven Press, New York 1978).
Guillemin, R.T.; Varga, J.; Rossier, S.; Minick, N.; Ling, C; Rivier, W.; Vale, W. and Bloom, F.: β-Endorphin and adreno-corticotropin are secreted concomitantly by the pituitary gland. Science 197: 1367–1369(1977).
Haier, R.J.; Quaid, K. and Mills, J.S.C.: Naloxone alters pain perception after jogging. Psychiatric Research 5: 231–232 (1981).
Hartley, L.H.; Mason, J.W.; Hogan, R.P.; Jones, L.G.; Kotchen, T.A.; Mougey, E.H.; Wherry, F.E.; Pennington, L.L. and Ricketts, P.T.: Multiple hormonal responses to prolonged exercise in relation to physical training. Journal of Applied Physiology 33: 607–610(1972).
Holaday, J.W.; Loh, H. and Li, C.H.: Unique behavioral effects of β-endorphin and their relationship to thermoregulation and hypothalamic function. Life Sciences 22: 1525–1536(1978).
Hughes, J.: Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Research 88: 295–308(1975).
Hughes, J.; Smith, T.W; Kosterlitz, H.W.; Fothergill, L.A.; Morgan, B.A. and Morris, H.R.: Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258: 577–579(1975).
Kosterlitz, H.W. and Hughes, J.: The opiate receptor; in Goldstein (Ed.) The Opiate Narcotics: Neurochemical Mechanisms in Analgesia and Dependence, pp.245–250 (Pergamon Press, New York 1975).
Lemaire, I.; Tseng, R. and Lemaire, S.: Systemic administration of β-EP: Potent hypotensive effect involving a serotonergic pathway. Proceedings of the National Academy of Science of the U.S.A. 75: 6240–6242 (1978).
Li, C.H.: Lipotropin, a new active peptide from pituitary glands. Nature 201: 924(1964).
Li, C.H.: β-Endorphin: A pituitary peptide with potent morphinelike reactivity. Archives of Biochemistry and Biophysics 183: 592–604(1977).
Lundberg, J.M.; Hokfelt, T.; Fahrenkrug, J.; Nilsson, G. and Terenius, L.: Peptides in the cat carotid body (glomus caroticum): VIP-. enkephalin-, and substance P-like immunoreactivity. Acta Physiologica Scandinavica 107: 279–281 (1979).
Markoff, R.A.; Ryan, P. and Young, T.: Endorphins and mood changes in long-distance running. Medicine and Science in Sports and Exercise 14: 11–15 (1982).
Mayer, G.; Wessel, J. and Kobberling, J.: Failure of NAL to alter exercise-induced GH and PRL release in normal men. Clinical Endocrinology (Oxford) 13: 413–416 (1980).
McArthur, J.W.: Endorphins and exercise in females: Possible connection with reproductive dysfunction. Medicine and Science in Sports and Exercise. (In press, 1984).
McArthur, J.W.; Bullen, B.A.; Beitins, I.Z.; Pagano, M.; Badger, T.M. and Klibanski, A.: Hypothalamic amenorrhea in runners of normal body composition. Endocrinology Research Communications 7: 13–25(1980).
McDonald, R.K.; Evans, F.T.; Weise, V.K. and Patrick, R.W.: Effect of morphine and naloxone on plasma hydrocortisone levels in man. Journal of Pharmacological Experimental Therapeutics 125: 241–247 (1959).
McNair, D.M.; Lorr, M. and Droppleman, L.F.: Profile of Mood States Manual (Educational and Industrial Testing Service, San Diego 1971).
McQueen, D.S.: Opioid interactions with respiratory and circulatory systems. British Medical Bulletin 39: 77–82 (1983).
Meites, J.: Relation of endogenous opioid peptides to secretion of hormones. Federation Proceedings 39: 2531–2532 (1980).
Meyerson, B.J. and Terenius, L.: β-EP and male sexual behaviour. European Journal of Pharmacology 42: 191–192 (1977).
Moretti, C.; Fabbri, A.; Gnessi, L; Cappa, M.; Calzolari, A.; Fraioli, F.; Grossman, A. and Besser, G.M.: NAL inhibits exercise-induced release of PRL and GH in athletes. Clinical Endocrinology (Oxford) 18: 135–138 (1983).
Morgan, W.P.: Exercise-induced euphoria: Fact or fancy? Medicine and Science in Sports and Exercise. (In press, 1984).
Morley, J.E.: The neuroendocrine control of appetite: The role of endogenous opiates, cholecystokinin, TRH, gamma-amino butyric acid and the diazepam receptor. Life Sciences 27: 335–368 (1980).
Morley, J.E.: The endocrinology of the opiates and opioid peptides. Metabolism 30: 195–209 (1981).
Morley, J.E. and Levine, A.S.: Stress-induced eating is mediated through endogenous opiates. Science 209: 1259–1261 (1980).
Moss, I.R. and Friedman, E.: β-EP: Effects on respiratory regulation. Life Sciences 23: 1271–1276 (1978).
Nakao, K.; Nakai, Y.; Oki, S.; Matsubara, S.; Konishi, T.; Nishitani, H. and Imura, H.: Immunoreactive β-endorphin in human cerebrospinal fluid. Journal of Endocrinology and Metabolism 50: 230–233 (1980).
Oyama, T.; Jin, T.; Yamaya, R.; Ling, N. and Guillemin, R.: Profound analgesic effects of β-endorphin in man. Lancet 1: 122–124 (1980).
Paton, W.D.M.: The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea pig ileum. British Journal of Pharmacology and Chemotherapy 12: 119–127 (1957).
Prior, J.C.; Ho Yuen, B.; Jensen, L.; Brownlie, L. and Haggis, H.: Controlled study of pituitary and gonadal stimulation during control and exercise menstrual cycles in normal women. Clinical and Investigative Medicine 4: 16B (1981).
Quigley, M.E. and Yen, S.S.: The role of endogenous opiates on LH secretion during the menstrual cycle. Journal of Clinical Endocrinology and Metabolism 51: 179–181 (1980).
Reid, R.L.; Hoff, J.D.; Yen, S.S.C. and Li, C.H.: Effects of exogenous β-endorphin on pituitary hormone secretion and its disappearance rate in normal human subjects. Journal of Clinical Endocrinology and Metabolism 52: 1179–1184 (1981).
Reith, P.; Byrd, P.; Silver, B.; Kyner, J. and Thomas, T.R.: Pre-menarchial hormonal pattern in lean athletic women with secondary amenorrhea. Medicine and Science in Sports and Exercise 14: 145 (1982).
Rennie, M.J.; Jennett, S. and Johnson, R.H.: The metabolic effects of strenuous exercise: A comparison between untrained subjects and racing cyclists. Quarterly Journal of Experimental Physiology 59: 201–212 (1974).
Ropert, J.F.; Quigley, M.E. and Yen, S.S.C.: Endogenous opiates modulate pulsatile LH release in humans. Journal of Clinical Endocrinology and Metabolism 52: 583–585 (1981).
Santen, R.J.; Sofsky, J.; Bilic, N. and Lippert, R.: Mechanism of action of narcotics in the production of menstrual dysfunction in women. Fertility and Sterility 26: 538–548 (1975).
Schaumann, W.: Inhibition by morphine of the release of acetylcholine from the intestine of the guinea pig. British Journal of Pharmacology and Chemotherapy 12: 115–118 (1957).
Schwartz, B.; Cumming, D.C.; Riordan, E.; Selye, M.; Yen, S.S.C. and Rebar, R.W.: Exercise-associated amenorrhea: A distinct entity? American Journal of Obstetrics and Gynecology 141: 662–670 (1981).
Shangold, M.; Freeman, R.; Thysen, B. and Gatz, M.: The relationship between long-distance running, plasma P and luteal phase length. Fertility and Sterility 31: 130–133 (1979).
Simantov, R.; Goodman, R.; Aposhian, D. and Snyder, S.H.: Phylogenetic distribution of a morphine-like peptide enkephalin. Brain Research 111: 204–211 (1976).
Spiler, I.J. and Molitch, M.E.: Lack of modulation of pituitary hormone stress response by neural pathways involving opiate receptors. Journal of Clinical Endocrinology 50: 516–520 (1980).
Stephen, G.W.; Cooper, L.V. and Harvey, D.: The effect of narcotic-antagonist drugs in the newborn rabbit. British Journal of Anaesthesia 48: 635–637 (1976).
Stubbs, W.A., Jones, A.; Edwards, C.R.W.; Delitala, G.; Jeffcoate, W.J.; Ratter, S.J.; Besser, G.M.; Bloom, S.R. and Alberti, K.G.M.M.: Hormonal and metabolic responses to an enkephalin analogue in normal man. Lancet 2: 1225–1227 (1978).
Sutton, J.R.: Endorphins and the physiological and metabolic responses to exercise. Medicine and Science in Sports and Exercise. (In press, 1984).
Sutton, J.R.; Brown, G.M.; Keane, P.; Walker, W.H.C.; Jones, N.L.; Rosenbloom, D. and Besser, G.M.: The role of endorphins in the hormonal and psychological responses to exercise. International Journal of Sports Medicine 2: 19 (1982).
Sutton, J.R. and Jones, N.L.: Control of pulmonary ventilation during exercise and mediators in the blood: CO: and hydrogen ion. Medicine and Science in Sports 11: 198–203 (1979).
Sutton, J.R.; Young, J.D.; Lazarus, L.; Hickie, J.B. and Maksvytis, J.: The hormonal response to physical exercise. Australasian Annals of Medicine 18: 84–90 (1969).
Terenius, L. and Wahlstrom, A.: Inhibitors of narcotic receptor binding in brain extracts and cerebrospinal fluid. Acta Pharmacologica et Toxicologica 35 (Suppl. 87): 55 (1974).
Terjung, R.: Endocrine response to exercise; in Hutton (Ed.) Exercise and Sports Sciences Reviews 7: 153–180 (Franklin Institute Press, Philadelphia 1979).
Tharp, G.D.: The role of glucocorticoids in exercise. Medicine and Science in Sports 7: 6–11 (1975).
Tolis, G.; Hickey, J. and Guyda, H.: Effects of morphine, Cortisol, PRL and TSH in man. Journal of Clinical Endocrinology and Metabolism 41: 797–800 (1975).
Vale, W.; Spiess, J.; Rivier, C. and Rivier, J.: Characterization of a 42-residuc ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213: 1394–1397 (1981).
Volavka, J.; Bauman, J.; Pevnick, J.; Reker, D.; James, B. and Cho, D.: Short-term hormonal effects of NAL in man. Psychneuroendocrinology 5: 225–234 (1980).
Volavka, J.; Cho, D.; Mallya, A. and Bauman, J.: Naloxone increases ACTH and Cortisol levels in man. New England Journal of Medicine 300: 1056–1057 (1979).
Von Graffenried, B.; del Pozo, E.; Roubicek, J.; Krebs, E.; Poldinger, W.; Burmeister, P. and Kerp, L.: Effects of the synthetic analogue FK 33-824 in man. Nature 272: 729–730 (1978).
Wahren, J.: Metabolic adaptation to physical exercise in man; in DeGroot et al. (Eds) Endocrinology, pp. 1911–1926 (Grune and Stratton, New York 1979).
Warren, M.P.: The effects of exercise on pubertal progression and reproductive function in girls. Journal of Clinical Endocrinology and Metabolism 51: 1150–1156 (1980).
Wehrenberg, W.B.; Wardlaw, S.L.; Frantz, A.G. and Ferin, M.: β-Endorphin in hypophyseal portal blood: Variations throughout the menstrual cycle. Endocrinology 111: 879–881 (1982).
Wharton, J.; Polak, J.M.; Pearse, A.G.E.; McGregor, G.P.; Bryant, M.G.; Bloom, S.R.; Emson, P.C.; Bisgard, G.E. and Will, J.A.: Enkephalin-, VIP-, and substance P-like immunoreactivity in the carotid body. Nature 284: 269–271 (1980).
Wildt, L.; Niesert, S.; Wesner, G. and Layendecker, G.: Effects of naloxone on LH, FSH and prolactin secretion in hypothalamic amenorrhea. Acta Endocrinologica 97 (Suppl. 243): 52 (1981).
Yates, A.; Leehey, K. and Shisslak, C.M.: Running — an analogue of anorexia? New England Journal of Medicine 308: 251–255 (1983).
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Harber, V.J., Sutton, J.R. Endorphins and Exercise. Sports Medicine 1, 154–171 (1984). https://doi.org/10.2165/00007256-198401020-00004
- Luteinising Hormone
- Opioid Peptide
- Clinical Endocrinology
- Endogenous Opioid