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. 1976 Jun;57(6):1393–1402. doi: 10.1172/JCI108408

Suppression by cyproheptadine of human growth hormone and cortisol secretion during sleep.

K Chihara, Y Kato, K Maeda, S Matsukura, H Imura
PMCID: PMC436797  PMID: 180050

Abstract

The effect of cyproheptadine on plasma growth hormone and cortisol levels was studied in seven male volunteers with polygraphic sleep monitoring. Sleep-related growth hormone release was completely inhibited in three of the seven normal subjects by the intravenous infusion of cyproheptadine (5 mg) which was started at the onset of sleep. In the other four, growth hormone release during sleep was significantly decreased or delayed by cyproheptadine when the drug infusion was started at 7:00 p.m., 1-2 h before the onset of sleep. The usual increase in plasma cortisol in the early morning was completely suppressed in all five subjects given cyproheptadine infusions from 4:00 to 7:00 a.m. The intravenous infusion of cyproheptadine increased slow wave sleep, although the time from sleep onset to the first occurrence of slow wave sleep was not affected. In contrast, rapid eye movement sleep was significantly decreased by cyproheptadine. These results suggest that cyproheptadine inhibits growth hormone and ACTH secretion during sleep in man, possibly by antagonizing serotoninergic mechanisms although other actions of the drug are not ruled out.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bivens C. H., Lebovitz H. E., Feldman J. M. Inhibition of hypoglycemia-induced growth hormone secretion by the serotonin antagonists cyproheptadine and methysergide. N Engl J Med. 1973 Aug 2;289(5):236–239. doi: 10.1056/NEJM197308022890503. [DOI] [PubMed] [Google Scholar]
  2. Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
  3. Chakrabarty A. S., Pillai R. V., Anand B. K., Singh B. Effect of cyproheptadine on the electrical activity of the hypothalamic feeding centres. Brain Res. 1967 Nov;6(3):561–569. doi: 10.1016/0006-8993(67)90066-2. [DOI] [PubMed] [Google Scholar]
  4. Chihara K., Kato Y., Maeda K., Ohgo S., Imura H. Suppressive effect of L-dopa on human prolactin release during sleep. Acta Endocrinol (Copenh) 1976 Jan;81(1):19–27. doi: 10.1530/acta.0.0810019. [DOI] [PubMed] [Google Scholar]
  5. Collu R., Fraschini F., Visconti P., Martini L. Adrenergic and serotoninergic control of growth hormone secretion in adult male rats. Endocrinology. 1972 May;90(5):1231–1237. doi: 10.1210/endo-90-5-1231. [DOI] [PubMed] [Google Scholar]
  6. Dunleavy D. L., Brezinova V., Oswald I., Maclean A. W., Tinker M. Changes during weeks in effects of tricyclic drugs on the human sleeping brain. Br J Psychiatry. 1972 Jun;120(559):663–672. doi: 10.1192/bjp.120.559.663. [DOI] [PubMed] [Google Scholar]
  7. Honda Y., Takahashi K., Takahashi S., Azumi K., Irie M., Sakuma M., Tsushima T., Shizume K. Growth hormone secretion during nocturnal sleep in normal subjects. J Clin Endocrinol Metab. 1969 Jan;29(1):20–29. doi: 10.1210/jcem-29-1-20. [DOI] [PubMed] [Google Scholar]
  8. Imura H., Nakai Y., Yoshimi T. Effect of 5-hydroxytryptophan (5-HTP) on growth hormone and ACTH release in man. J Clin Endocrinol Metab. 1973 Jan;36(1):204–206. doi: 10.1210/jcem-36-1-204. [DOI] [PubMed] [Google Scholar]
  9. Jouvet M. The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle. Ergeb Physiol. 1972;64:166–307. doi: 10.1007/3-540-05462-6_2. [DOI] [PubMed] [Google Scholar]
  10. Krieger D. T., Amorosa L., Linick F. Cyproheptadine-induced remission of Cushing's disease. N Engl J Med. 1975 Oct 30;293(18):893–896. doi: 10.1056/NEJM197510302931802. [DOI] [PubMed] [Google Scholar]
  11. Krieger D. T., Rizzo F. Serotonin mediation of circadian periodicity of plasma 17-hydroxycorticosteroids. Am J Physiol. 1969 Dec;217(6):1703–1707. doi: 10.1152/ajplegacy.1969.217.6.1703. [DOI] [PubMed] [Google Scholar]
  12. Krieger H. P., Krieger D. T. Chemical stimulation of the brain: effect on adrenal corticoid release. Am J Physiol. 1970 Jun;218(6):1632–1641. doi: 10.1152/ajplegacy.1970.218.6.1632. [DOI] [PubMed] [Google Scholar]
  13. Lucke C., Glick S. M. Experimental modification of the sleep-induced peak of growth hormone secretion. J Clin Endocrinol Metab. 1971 Jun;32(6):729–736. doi: 10.1210/jcem-32-6-729. [DOI] [PubMed] [Google Scholar]
  14. Maeda K., Kato Y., Ohgo S., Chihara K., Yoshimoto Y., Yamaguchi N., Kuromaru S., Imura H. Growth hormone and prolactin release after injection of thyrotropin-releasing hormone in patients with depression. J Clin Endocrinol Metab. 1975 Mar;40(3):501–505. doi: 10.1210/jcem-40-3-501. [DOI] [PubMed] [Google Scholar]
  15. Mendelson W. B., Jacobs L. S., Reichman J. D., Othmer E., Cryer P. E., Trivedi B., Daughaday W. H. Suppression of sleep-related prolactin secretion and enhancement of sleep-related growth hormone secretion. J Clin Invest. 1975 Sep;56(3):690–697. doi: 10.1172/JCI108139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murphy B. E. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. doi: 10.1210/jcem-27-7-973. [DOI] [PubMed] [Google Scholar]
  17. Nakai Y., Imura H., Sakurai H., Kurahachi H., Yoshimi T. Effect of cyproheptadine on human growth hormone secretion. J Clin Endocrinol Metab. 1974 Mar;38(3):446–449. doi: 10.1210/jcem-38-3-446. [DOI] [PubMed] [Google Scholar]
  18. Nakai Y., Imura H. Suppressive effect of cyproheptadine on L-DOPA-induced growth hormone release in man. Endocrinol Jpn. 1975 Aug;22(4):357–360. doi: 10.1507/endocrj1954.22.357. [DOI] [PubMed] [Google Scholar]
  19. Naumenko E. V. Hypothalamic chemoreactive structures and the regulation of pituitary-adrenal function. Effects of local injections of norepinephrine, carbachol and serotonin into the brain of guinea pigs with intact brains and after mesencephalic transection. Brain Res. 1968 Oct;11(1):1–10. doi: 10.1016/0006-8993(68)90069-3. [DOI] [PubMed] [Google Scholar]
  20. Parker D. C., Rossman L. G., Siler T. M., Rivier J., Yen S. S., Guillemin R. Inhibition of the sleep-related peak in physiologic human growth hormone release by somatostatin. J Clin Endocrinol Metab. 1974 Mar;38(3):496–499. doi: 10.1210/jcem-38-3-496. [DOI] [PubMed] [Google Scholar]
  21. Parker D. C., Sassin J. F., Mace J. W., Gotlin R. W., Rossman L. G. Human growth hormone release during sleep: electroencephalographic correlation. J Clin Endocrinol Metab. 1969 Jun;29(6):871–874. doi: 10.1210/jcem-29-6-871. [DOI] [PubMed] [Google Scholar]
  22. Plonk J. W., Bivens C. H., Feldman J. M. Inhibition of hypoglycemia-induced cortisol secretion by the serotonin antagonist cyproheptadine. J Clin Endocrinol Metab. 1974 May;38(5):836–840. doi: 10.1210/jcem-38-5-836. [DOI] [PubMed] [Google Scholar]
  23. Quabbe H. J., Schilling E., Helge H. Pattern of growth hormone secretion during a 24-hour fast in normal adults. J Clin Endocrinol Metab. 1966 Oct;26(10):1173–1177. doi: 10.1210/jcem-26-10-1173. [DOI] [PubMed] [Google Scholar]
  24. Sassin J. F., Parker D. C., Mace J. W., Gotlin R. W., Johnson L. C., Rossman L. G. Human growth hormone release: relation to slow-wave sleep and sleep-walking cycles. Science. 1969 Aug 1;165(3892):513–515. doi: 10.1126/science.165.3892.513. [DOI] [PubMed] [Google Scholar]
  25. Smythe G. A., Lazarus L. Growth hormone regulation by melatonin and serotonin. Nature. 1973 Jul 27;244(5413):230–231. doi: 10.1038/244230a0. [DOI] [PubMed] [Google Scholar]
  26. Smythe G. A., Lazarus L. Suppression of human growth hormone secretion by melatonin and cyproheptadine. J Clin Invest. 1974 Jul;54(1):116–121. doi: 10.1172/JCI107732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. TICKNER A. Inhibition of amine oxidase by antihistamine compounds and related drugs. Br J Pharmacol Chemother. 1951 Dec;6(4):606–610. doi: 10.1111/j.1476-5381.1951.tb00671.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Takahashi Y., Kipnis D. M., Daughaday W. H. Growth hormone secretion during sleep. J Clin Invest. 1968 Sep;47(9):2079–2090. doi: 10.1172/JCI105893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wyatt R. J., Engelman K., Kupfer D. J., Scott J., Sjoerdsma A., Snyder F. Effects of para-chlorophenylalanine on sleep in man. Electroencephalogr Clin Neurophysiol. 1969 Nov;27(5):529–532. doi: 10.1016/0013-4694(69)90193-x. [DOI] [PubMed] [Google Scholar]
  30. Wyatt R. J., Zarcone V., Engelman K., Dement W. C., Snyder F., Sjoerdsma A. Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroencephalogr Clin Neurophysiol. 1971 Jun;30(6):505–509. doi: 10.1016/0013-4694(71)90147-7. [DOI] [PubMed] [Google Scholar]
  31. van Riezen H. Different central effects of the 5-HT antagonists mianserine and cyproheptadine. Arch Int Pharmacodyn Ther. 1972 Aug;198(2):256–269. [PubMed] [Google Scholar]

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