Abstract
The metyrapone-test was used to study the influence of pituitary-adrenal activity on the pineal function in man. We recorded in blood the circadian rhythmicity of melatonin, ACTH and Cortisol and the excretion of melatonin, Cortisol and Porter-Silber chromogens in urine before, during and after the administration of 750 mg metyrapone every 4 h during 24 h in two healthy volunteers and in two patients with asymptomatic, moderate hyperparathyroidism and a prolactin-secreting microadenoma, respectively. The present study confirmed our previous report on an increased excretion of melatonin per 24 h and per mmol creatinine during the administration of metyrapone. The excretory maximum preceded the maximal ACTH-adrenal response. Serum melatonin remained unchanged during the administration of metyrapone. A second finding was depressed serum melatonin the night after the test in the subjects with the most marked ACTH-cortisol response following the metyrapone-test indicating suppression of melatonin secretion when ACTH-cortisol secretions were increased. A third finding was a late increase in diuresis appearing the day after metyrapone-administration while glomerular filtration rates did not show significant alterations. Thus, it is shown that the metyrapone-induced Cortisol inhibition stimulates both ACTH and melatonin secretion, while high ACTH and Cortisol levels are accompanied by reduced S-melatonin levels.
Similar content being viewed by others
References
Wurtman R.J., Shein H.M., Larin F. Mediation by beta-adrenergic receptors of effect of norepinephrine on pineal synthesis of 14C-serotonin and 14C-melatonin. J. Neurochem. 18: 1683, 1971.
Wetterberg L. Melatonin in humans, physiological and clinical studies. J. Neurol. Transm. 13: 280, 1978.
Werner S., Brismar K., Wetterberg L. Eneroth P. Circadian rhythms of melatonin, prolactin, growth hormone and Cortisol in patients with pituitary adenomas due to adrenal tumours. In: Birau N., Schloot W. (Eds.), Advances in the biosciences, vol. 29, Melatonin: Current status and perspectives. Pergamon Press, Oxford and New York, 1980, p. 357.
Wetterberg L. Eriksson O. Friberg V. Vangbo B. A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half life of plasma melatonin in man. Clin. Chim. Acta 86: 169, 1980.
Wetterberg L., Aperia V., Beck-Friis J., Kjellman B.F., Ljunggren J.-C, Nilsonne P., Pettersson U., Tham A., Undén F. Melatonin and Cortisol levels in psychiatric illness. Lancet 2: 100, 1982.
Wetterberg L., Beck-Friis J., Kjellman B.F., Ljunggren J.-G. Circadian rhythms in melatonin and Cortisol secretion in depression. In: F. Sjōkvist, M. Åsberg, E. Usdin (Eds.), Frontiers in biochemical and pharmacological research in depression. Nobel Conference, Stockholm, Sweden, June 18–19, Raven Press, London, New York, 1982.
Brismar K., Werner S., Wetterberg L. Melatonin and corticosteroid response to metyrapone in patients with pituitary disease. In: R.S. Reiter (Ed.), The pineal and its hormones. Alan & Liss Inc., New York, 1982, p. 283.
Thorén M., Ajne M., Hall K. Plasma pattern of immunoreactive ACTH in normal men and in patients with Nelson’s syndrome. Acta Endocrinol. (Kbh.) 96: 15, 1981.
Silber R.H., Porter C.C. The determination of 17, 21-dihydroxy-20 ketosteroids in urine and plasma. J. Biol. Chem. 210: 293, 1954.
Bruno O.D., Leclerq R., Virasoro E., Copinschi G. Extraadrenal actions of metyrapone in man. Effects on plasma Cortisol disappearance, growth hormone secretion and glucose metabolism. J. Clin. Endocrinol. Metab. 32: 260, 1971.
Takahara J., Ogawa N., Ofujii T. Extraadrenal action of metyrapone upon human growth secretion in man. Endocrinol. Jpn. 19: 197, 1972.
Levin J., Zumoff V., Fukushima D.K. Extraadrenal effects of metyrapone in man. J. Clin. Endocrinol. Metab. 47: 845, 1978.
Hildebrandt A.G. The binding of metyrapone to cytochrome p-450 and its inhibitory action on microsomal hepatic mixed function oxidation reactions. Biochem. Soc. Symp. 34: 79, 1972.
Simon S., Kahl G.G., Nettler K.J. Beeinflussung von Redoxstatus und Sauerstoffverbrauch isoliert perfundierter Rattenlebern durch Mety-rapon. Naunyn Schmiedebergs Arch. Pharmacol. 226: 454, 1970.
Arendt J., Wetterberg L., Heyden T., Sizonenko P.C., Paunier L. Radioimmunoassay of melatonin: human serum and cerebrospinal fluid. Horm. Res. 8: 65, 1977.
von Szadkowski D., Jorgensen A., Essing H.G., Schaller K.H. Die Kreatinnelimitations rate also Bezugsgrösse für Analysen aus Harnprobelm. Z. Klin. Chem. Klin. Biochem. 8: 529, 1970.
Touitou Y., Bodgan M., Limai J.M., Touitou C., Reinberg A. Circadian rhythms in urinary steroids in response to a 36-hour sustained metyrapone administration in young men. Horm. Metab. Res. 9: 314, 1977.
Shotman P., Allaart J., Gispen W.H. Pineal protein synthesis highly sensitive to ACTH-like neuropeptides. Brain Res. 219: 121, 1981.
Cardinali D.P., Vacas M.I. Feedback control of pineal function by reproductive hormones — A neuroendocrine paradigm. J. Neurol. Transm. (Suppl.) 13: 175, 1978.
Yuwiler A., Brammer G.L. Neonatal hormone treatment and maturation of the pineal noradrenergic system: hydrocortisone and thyroxine. J. Neurochem. 37: 985, 1981.
De Fronzo R.A., Roth W.D. Evidence for the existence of pineal adrenal and a pineal-thyroid axis. Acta Endocrinol. (Kbh.) 70: 31, 1972.
Nir I. Non-reproductive systems and the pineal gland. J. Neurol. Transm. (Suppl.) 13: 225, 1978.
Heiman M.L., Porter J.R. Inhibitory effects of a pineal extract on adrenal cortex. Lack of competition with ACTH. Horm. Res. 12: 104, 1980.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brismar, K., Werner, S., Thorén, M. et al. Metyrapone: an agent for melatonin as well as ACTH and Cortisol secretion. J Endocrinol Invest 8, 91–95 (1985). https://doi.org/10.1007/BF03350653
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03350653