Abstract
Opiates stimulate the growth hormone and prolactin responses to stimuli in non-obese humans. Obese patients, however, show lowered growth hormone and prolactin responses and raised β-endorphin levels. We therefore investigated the effect of the opiate antagonist naloxone on the stimulated growth hormone and prolactin secretions in a controlled double-blind study in obese patients. All patients received 200µg TRH and 0.5 g/kg b.w. arginine together with 2 mg of naloxone or placebo i.v. in a randomized sequence. The TRH- and arginine-induced increases in prolactin and growth hormone were significantly greater after administration of naloxone (p < 0.05). Naloxone also produced a significant increase in ACTH, Cortisol and β-endorphin when compared with placebo. TSH, triiodothyronine, thyroxine, insulin, glucagon and blood glucose showed no significant differences between both days of the trial. The effect of naloxone on growth hormone and prolactin secretions in obese humans can thus be regarded as a partial normalization. We therefore conclude that the hypothalamic regulatory disturbance of growth hormone and prolactin secretions in the obese could be caused by raised opiate levels.
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Morley J.E. The endocrinology of the opiates and the opiate peptides. Metabolism 30: 195, 1981.
Tolis G., Hickey J., Guyda H. Effects of morphine on serum growth hormone, Cortisol, prolactin and thyroid stimulating hormone in man. J. Clin. Endocrinol. Metab. 41: 797, 1975.
Delitala G., Grossman A., Besser M. Differential effects of opiate peptides and alkaloids on anterior pituitary hormone secretion. Neuroendocrinology 37: 275, 1983.
Stubbs W.A., Delitala G., Jones A., Jeffcoate W.J., Edwards C.R.W., Ratter S.J., Besser G.M., Bloom S.R., Alberti K.G.M.M. Hormonal and metabolic responses to an enkephalin analogue in normal men. Lancet 2: 1225, 1978.
Grossman A., Stubbs W.A., Gaillard R.C., Delitala G., Rees L.H., Besser G.M. Studies of the opiate control of prolactin, GH and TSH. Clin. Endocrinol. (Oxf.) 14: 381, 1981.
Demura R., Suda T., Wakabayashi I., Yoshimura M., Jibiki K., Odagiri E., Demura H., Shimuze K. Plasma pituitary hormone response to the synthetic enkephalin analog (FK33-824) in normal subjects and patients with pituitary diseases. J. Clin. Endocrinol. Metab. 52: 263, 1981.
Reid R.L., Hoff J.D., Yen S.S.C., Li C.H. Effects of exogenous β-endorphin on pituitary hormone secretion and its disappearance rate in normal subjects. J. Clin. Endocrinol. Metab. 52: 1179, 1981.
Morley J.E., Baranetsky N.G., Wingert T.D., Carlson H.E., Hersham J.E., Melmed S., Levin S.R., Jamison K.R., Weitzman R., Chang J., Varner A.A. Endocrine effects of naloxone-induced opiate receptor blockade. J. Clin. Endocrinol. Metab. 50: 251, 1980.
Spiler I.J., Molitch M.E. Lack of modulation of pituitary hormone stress response by neural pathways involving opiate receptors. J. Clin. Endocrinol. Metab. 50: 516, 1980.
Martin J.B., Tolis G., Wood I., Guyda H. Failure of naloxone to influence physiological growth hormone and prolactin secretion. Brain Res. 168: 210, 1979.
Pontiroli A.E., Baio G., Stella L., Crescenti A., Girardi A.M. Effects of naloxone on prolactin, luteinizing hormone and Cortisol responses to surgical stress in humans. J. Clin. Endocrinol. Metab. 55: 378, 1982.
Moretti C., Fabbri A., Gnessi L., Cappa M., Calzolari A., Fraioli F., Grossman A., Besser G.M. Naloxone inhibits exercise-induced release of PRL and GH in athletes. Clin. Endocrinol. (Oxf.) 18: 135, 1983
Wakabayashi I., Demura R., Miki N., Ohmura E., Miyoshi H., Shizume K. Failure of naloxone to influence plasma growth hormone, prolactin, and Cortisol secretions induced by insulin hypoglycemia. J. Clin. Endocrinol. Metab. 50: 597, 1980.
Mayer G., Wessel J., Köbberling J. Failure of naloxone to alter exercise-induced growth hormone and prolactin release in normal men. Clin. Endocrinol. (Oxf.) 13: 413, 1980.
Grossman A., Bouloux P., Price P., Drury P.L., Lam K.S.L., Turner T., Thomas J., Besser G.M., Sutton J. The role of opioid peptides in the hormonal responses to acute exercise in man. Clin. Sci. 67: 483, 1984.
Copinschi J.R., Wegienka L.C., Hane S., Forsham P.H. Effect of arginine on serum levels of insulin and growth hormone in obese subjects. Metabolism 16: 485, 1967.
Kopelman P.G., White N., Pilkington T.R.E., Jeffcoate S.L. Impaired hypothalamic control of prolactin secretion in massive obesity. Lancet 1: 747, 1979.
Jung R.T., Campbell R.G., James W.P., Callingham B.A. Altered hypothalamic and sympathetic responses to hypoglycemia in familial obesity. Lancet 1: 1043, 1982.
Williams T., Berelowitz M., Joffe S.N., Thorner M., Rivier J., Vale W., Frohman L.A. Impaired growth hormone response to growth hormone-releasing factor in obesity: a pituitary defect reversed with weight reduction. N. Engl. J. Med. 311: 1403, 1984.
Givens J.R., Wiedemann E., Andersen R.N., Kitabchi A.E. β-endorphin and β-lipotropin plasma levels in hirsute women: correlation with body weight. J. Clin. Endocrinol. Metab. 50: 975, 1980.
Genazzani A.R., Facchinetti F., Petraglia F., Pintor G., Corda C. Hyperendorphinemia in obese children and adolescents. J. Clin. Endocrinol. Metab. 62: 36, 1986.
Reid R.L., Yen S.S.C. β-endorphin stimulates the secretion of insulin and glucagon in humans. J. Clin. Endocrinol. Metab. 52: 592, 1981.
Feldman M., Kiser R.S., Unger R.H., Li C.H. β-endrophin and exocrine pancreas. Studies in healthy and diabetic human beings. N. Engl. J. Med. 308: 349, 1983.
Copinschi G., Cornie A., Leclercq R., Frankson J.R.M. Cortisol secretion rate and urinary corticoid excretion in normal and obese subjects. Acta Endocrinol. (Kbh.) 51: 186, 1966.
Ceresa F., Angeli A., Boccuzzi G., Perotti L. Impulsive and basal ACTH secretion phases in normal subjects, in obese subjects with signs of adrenocortical hyperfunction and in hyperthyroid patients. J. Clin. Endocrinol. Metab. 31: 491, 1970.
Casper R.F., Bhanot R., Wilkinson M. Prolonged elevation of hypothalamic opioid peptide activity in woman taking oral contraceptives. J. Clin. Endocrinol. Metab. 58: 582, 1984.
Cetel N.S., Quigley M.R., Yen S.S.C. Naloxone-induced prolactin secretion in women: evidence against a direct prolactin stimulatory effect of endogenous opioids. J. Clin. Endocrinol. Metab. 60: 191, 1985.
Casper R.F., Yen S.S.C. Simultaneous pulsatile release of prolactin and luteinizing hormone induced by luteinizing hormone-releasing factor. J. Clin. Endocrinol. Metab. 52: 934, 1981.
Naber D., Pickar D., Davis G.C., Cohen R.M., Jimerson D.C., Elchisak M.A., Defraites E.G., Kalin N.H., Risch S.C., Buchsbaum M.S. Naloxone effects on β-endorphin, Cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. Psychopharmacology 74: 125, 1981.
Janowsky D.J., Judd L., Hyet L., Roitman N., Parker D. Naloxone effects on serum growth hormone and prolactin in man. Psychopharmacology 65: 95, 1979.
Guillemin R., Vargo T., Rossier J., Minick S., Ling N., Rivier C., Vale W., Bloom F. β-endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197: 1367, 1977.
Paterson S.J., Robson L.E., Kosterlitz H.W. Classification of opioid receptors. Br. Med. Bull. 39: 31, 1983.
Levin E.R., Yamada T., Levin S., Mills S. Endogenous opioid modulation of pancreatic hormone secretion: studies in dogs. Metabolism 35: 59, 1986.
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Plewe, G., Schneider, U., Krause, U. et al. Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans. J Endocrinol Invest 10, 137–141 (1987). https://doi.org/10.1007/BF03347177
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DOI: https://doi.org/10.1007/BF03347177