Differences in the Effects of Acute and Chronic Administration of Dexfenfluramine on Cortisol and Prolactin Secretion

  • C. Oliver
  • D. Ježová
  • M. Grino
  • V. Guillaume
  • F. Boudouresque
  • B. Conte-Devolx
  • G. Pesce
  • A. Dutour
  • D. Becquet
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 274)


The involvement of serotonin on neuroendocrine regulation has been substantiated by much experimental data. Indeed, serotonin has been shown to play a role in the regulation of pituitary hormones that display a secretory rhythmicity and/or changes after exposure by to various types of stress. These results are supported by the existence of a serotoninergic innervation of hypothalamic regions that control hormonal rhythmical secretion of hormones (suprachiasmatic nucleus) and that respond to stress (paraventricular nucleus) (1).


Plasma Cortisol Level Corticosterone Secretion Serotonin Agonist Index Body Weight Novelty Stress 
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  1. 1.
    Montange, M., and A. Calas, Serotonin and endocrinology, the pituitary, In N.N. Osborn and M. Hamon (eds) Neuronal Serotonin ,Wiley & Sons, New York, pp. 271–303, 1988.Google Scholar
  2. 2.
    Kyriakides, M., and T. Silverstone, Comparison of the effects of d-amphetamine and fenfluramine on hunger and food intake in man, Neuropharmacology 18: 1007–1008, 1979.PubMedCrossRefGoogle Scholar
  3. 3.
    Wurtman, J.J., and R.J. Wurtman, D-fenfluramine selectively decreases carbohydrate but not protein intake in obese subjects, Int J Obes 8: 79–84, 1984.PubMedGoogle Scholar
  4. 4.
    Garattini, S., W. Buczo, A. Jori, and R. Samanin, The mechanism of action of fenfluramine, Postgrad Med J 15: 27–35, 1975.Google Scholar
  5. 5.
    Leibowitz, S.F., G.F. Weiss, and G. Shor-Posner, Hypothalamic serotonin: pharmacological, biochemical, and behavioral analyses of its feed-suppressive action, Clin Neuropharmacol 11: S51–S71, 1988.PubMedGoogle Scholar
  6. 6.
    Kiss, J.Z., Dynamism of chemoarchitecture in the hypothalamic paraventricular nucleus, Brain Res Bull 20: 699–708, 1988.PubMedCrossRefGoogle Scholar
  7. 7.
    Fuller, R.W., and H.D. Snoddy, Effect of serotonin-releasing drugs on serum corticosterone in rats, Neuroendocrinology 31: 96–100, 1980.PubMedCrossRefGoogle Scholar
  8. 8.
    Koenig, J.I., G.A. Gudelsky, and H.Y. Meltzer, Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation, Eur J Pharmacol 137: 1–8, 1987.PubMedCrossRefGoogle Scholar
  9. 9.
    Lipolists, Zs., C. Phelix, and W.K. Pauli, Synaptic interaction of serotonergic axons and corticotropin-releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat, Histochemistry 86: 541–549, 1987.CrossRefGoogle Scholar
  10. 10.
    Feldman, S., N. Conforti, and E. Melamed, Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion, Brain Res Bull 18: 165–168, 1987.PubMedCrossRefGoogle Scholar
  11. 11.
    Van de Kar, L.D., J.H. Urban, K.D. Richardson, and C.L. Bethea, Pharmacological studies on the serotoninergic and nonserotonin-mediated stimulation of prolactin and corticosterone secretion by fenfluramine. Effects of pretreatment with fluoxetine, indalpine, PCPA, and L-tryptophan, Neuroendocrinology 41: 283–288, 1985.Google Scholar
  12. 12.
    McElroy, J.F., J.M. Miller, and J.S. Meyer, Fenfluramine, p-chloroamphetamine and p-fluoroamphetamine stimulation of pituitary-adrenocortical activity in rat: evidence for differences in site and mechanism of action, J Pharmacol Exper Ther 228: 593–599, 1984.Google Scholar
  13. 13.
    Porter, J.C., and K.R. Smith, Collection of hypophysial stalk blood in rat, Endocriology 81: 1182–1185, 1967.CrossRefGoogle Scholar
  14. 14.
    Ježová, D., R. Kvetňanský, K. Kovács, Z. Opršalová, M. Vigaš, and G.B. Makara, Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms, Endocrinology 120: 409–415, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Rowland, N.E., Effect of continuous infusions of dexfenfluramine on food intake, body weight and brain amines in rats, Life Sci 39: 2581–2586, 1986.PubMedCrossRefGoogle Scholar
  16. 16.
    Guillaume, V., B. Conte-Devolx, A. Szafarczyk, F. Malaval, N. Pares-Herbut, M. Grino, G. Alonso, I. Assenmacher, and C. Oliver, The corticotropin-releasing factor release in rat hypophysial portal blood is mediated by brain catecholamines, Neuroendocrinology 46: 143–146, 1987.PubMedCrossRefGoogle Scholar
  17. 17.
    Conte-Devolx, B., C. Oliver, P. Giraud, E. Castanas, F. Boudouresque, P. Gillioz, and Y. Millet, Adrenocorticotropin, β-endorphin and corticosterone secretion in Brattleboro rats, Endocrinology 110: 2097–2100, 1982.PubMedCrossRefGoogle Scholar
  18. 18.
    Gibbs, D.M., and W. Vale, Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood, Brain Res 280: 176–179, 1983.PubMedCrossRefGoogle Scholar
  19. 19.
    Holmes, M.C., G. Di Renzo, U. Beckford, B. Gillham, and M.T. Jones, Role of serotonin in the control of secretion of corticotrophin releasing factor, J Endocrinol 93: 151–160, 1982.PubMedCrossRefGoogle Scholar
  20. 20.
    Garattini S., S. Caccia, T. Mennini, R. Samanin, S. Consolo, and H. Ladinsky, Biochemical pharmacology of the anorectic drug fenfluramine: a review, Curr Med Res Opin 6: 15–27, 1979.CrossRefGoogle Scholar
  21. 21.
    Schwartz, D., L. Hernandez, and B.G. Hoebel, Fenfluramine administered systematically or locally increases extracellular serotonin in lateral hypothalamus as measured by microdialysis, Brain Res 482: 261–270, 1989.PubMedCrossRefGoogle Scholar
  22. 22.
    Heybach, J.P., and J. Vernikos-Danellis, Effects of fenfluramine administration on activity of the pituitary-adrenal system in the rat, West Pharmacol Soc Proc 21: 19–25, 1978.Google Scholar
  23. 23.
    Van de Kar, L.D., C.W. Wilkinson, Y. Skrobik, M.S. Brownfield, and W.F. Ganong, Evidence that serotonergic neurons in the dorsal raphe nucleus exert a stimulatory effect on the secretion of renin but not of corticosterone, Brain Res 235: 233–243, 1982.PubMedCrossRefGoogle Scholar
  24. 24.
    Van de Kar, L.D., C.W. Wilkinson, and W.F. Ganong, Pharmacological evidence for a role of brain serotonin in the maintenance of plasma renin activity in unanesthetized rats, J Pharmacol Exper Ther 219: 85–90, 1981.Google Scholar
  25. 25.
    Verhofstad, A.A.J., and G. Jonsson, Immunohistochemical and neurochemical evidence for the presence of serotonin in the adrenal medulla of the rat, Neuroscience 10: 1443–1453, 1983.PubMedCrossRefGoogle Scholar
  26. 26.
    Rácz, K., I. Wolf, R. Kiss, G. Lada, S. Vida, and E. Gláz, Corticosteroidogenesis by insolated human adrenal cells: effect of serotonin and serotonin antagonists, Experientia 35: 1532–1535, 1979.PubMedCrossRefGoogle Scholar
  27. 27.
    Serri, O, and E. Rasio, Effect of chronic administration of dextrofenfluramine (d-F) on prolactin (PRL) and corticosterone secretion and on central dopaminergic receptors, 70thAnnual Meeting of the Endocrine Society ,New Orleans, LA, June, Abstract 1177, p. 315, 1988.Google Scholar
  28. 28.
    Brindley, D.N. Metabolic and hormonal effects of dexfenfluramine on stress stiuations, Clin Neuropharmacol [Suppl 11] 1: S86–S89, 1988.Google Scholar
  29. 29.
    Yehuda, R., and J.S. Meyer, A role for serotonin in the hypothalamic-pituitary-adrenal response to insulin stress, Neuroendocrinology 38: 25–32, 1984.PubMedCrossRefGoogle Scholar
  30. 30.
    Szafarczyk, A., G. Ixart, F. Malaval, J. Nouguier-Soule, and I. Assenmacher, Effects of lesions of the suprachiasmatic nuclei and of p-chlorophenylalanine on the circadian rhythms of adrenocorticotrophic hormone and corticosterone in the plasma and on locomotor activity of rats, J Endocrinol 83:1–16,1979.PubMedCrossRefGoogle Scholar
  31. 31.
    Kopelman, P.G., Neuroendocrine function in obesity, Clin Endocrinol 28: 675–689, 1988.Google Scholar
  32. 32.
    Bernini, G.P., G.F. Argenio, M.S. Vivaldi, C. Del Corso, M. Sgro, F. Franchi, and M. Luisi, Effects of fenfluramine and ritanserin on prolactin response to insulin-induced hypoglycemia in obese patients: evidence for failure of the serotoninergic system, Horm Res 31: 133–137, 1989.PubMedCrossRefGoogle Scholar
  33. 33.
    Giaufre, E., B. Conte-Devolx, G. Morisson-Lacombe, F. Boudouresque, M. Grino, B. Rousset-Rouviere, V. Guillaume, and C. Oliver, Anesthesie peridurale par voie caudal chez l’enfant. Etude des variations endocriniennes, La Presse Médicale 14: 201–203, 1985.PubMedGoogle Scholar
  34. 34.
    Imura, H., Y. Nakai, and T. Yoshimi, Effect of 5-hydroxytryptophan (5-HTP) on growth hormone and ACTH release in man, J Clin Endocrinol Metab 36: 204–206, 1973.PubMedCrossRefGoogle Scholar
  35. 35.
    Modlinger, R.S, J.M. Schonmuller, and S.P. Arora, Adrenocorticotropin release by tryptophan in man, J Clin Endocrinol Metab 50: 360–363, 1980.PubMedCrossRefGoogle Scholar
  36. 36.
    Woolf, P.D., and L. Lee, Effects of the serotonin precursor, tryptophan, on pituitary hormone secretion, J Clin Endocrinol Metab 45: 123–133, 1977.PubMedCrossRefGoogle Scholar
  37. 37.
    Lewis, D.A., and B.M. Sherman, Serotonergic stimulation of adrenocorticotropin secretion in man, J Clin Endocrinol Metab 58: 458–462, 1984.PubMedCrossRefGoogle Scholar
  38. 38.
    Vague, J., P.H. Vague, J. Boyer, and M.C. Cloix, Antropometry of obesity. Diabetes, adrenal and beta-cell functions, In R.R. Rodriguez and J. Vallance-Owen (eds) Diabetes ,Excerpta Medica, Amsterdam, pp. 517–525, 1971.Google Scholar
  39. 39.
    Mashchak, CA., O.A. Kletzky, C. Spencer, and R. Artal, Transient effect of L-5-hydroxytryptophan on pituitary function in men and women, J Clin Endocrinol Metab 56: 170–176, 1983.PubMedCrossRefGoogle Scholar
  40. 40.
    Masala, A., G. Delitala, and L. Devilla, Enhancement of insulin-induced prolactin secretion by fluoxetine in man, J Clin Endocrinol Metab 49: 350–352, 1979.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • C. Oliver
    • 1
  • D. Ježová
    • 1
  • M. Grino
    • 1
  • V. Guillaume
    • 1
  • F. Boudouresque
    • 1
  • B. Conte-Devolx
    • 1
  • G. Pesce
    • 1
  • A. Dutour
    • 1
  • D. Becquet
    • 1
  1. 1.Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 297Faculté de Médecine NordMarseille Cédex 15France

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