Skip to main content
SpringerLink
Log in

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin, ACTH, and cortisol secretion

  • Original Papers
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

In a previous study we observed that calcitonin increases β-endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).

Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma β-endorphin, ACTH and cortisol were estimated every 30min from − 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at − 30 min and calcitonin i.v. at time 0. β-endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 μg/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time − 30 did not alter the response of β-endorphin, ACTH and cortisol to calcitonin (infused at time 0).

Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.

We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Becker KL, Sneider RH, Moore KG, Monogham Silva OL (1979) Calcitonin in extrapyramidal tissue in man. Acta Endocrinol 92: 746–751

    Google Scholar 

  • Buckingham JC, Hodges JR (1977) Hypothalamic polypeptides and analogous on corticotropin production by rat adenohypophyseal tissue in vitro. Br J Pharmacol 60: 298

    Google Scholar 

  • Buckingham JC, Hodges JR (1979) Hypothalamic receptors influencing the secretion of corticotropin releasing hormone in the rat. J Physiol (Lond) 290: 421–431

    Google Scholar 

  • Cavagnini F, Raggi U, Micosi P, Dilandro A, Invitti C (1976) Effect of antiserotonergic drug metergoline on the ACTH and cortisol response to insulin hypoglycemia and lysine vasopressin in man. J Clin Endocrinol Metab 43: 306–312

    Google Scholar 

  • Chihara K, Kato Y, Maeda K, Matsukara S, Imura H (1976) Suppression of cyproheptadine of human growth hormone and cortisol secretion during sleep. J Clin Invest 57: 1393–1402

    Google Scholar 

  • Cooper CW, Obie JF, Toverod SU, Munson PL (1977) Elevated calcitonin during suckling in the baby rat. Endocrinology 101: 1657–1664

    Google Scholar 

  • Delitala G (1982) Role of catecholaminergic neurotransmitters. In: Besser GM, Martini L (eds) Clinical neuroendocrinology. Academic Press, London, pp 1480

    Google Scholar 

  • Fabbri A, Santoro C, Moretti C et al (1981) The analgesic effect of calcitonin in humans: Studies on the role of opioid peptides. Int J Clin Pharmacol Ther Toxicol 19: 509–511

    Google Scholar 

  • Fisher JA, Tobler PH, Kaufmann M, Born W, Henke H, Cooper PE, Sagar SM, Martin JB (1981) Calcitonin regional distribution of the hormone and its binding sites in the human brain and pituitary. Proc Natl Acad Sci USA 78: 7801–7805

    Google Scholar 

  • Ganong WF (1980) Neurotransmitters and pituitary functions: regulation of ACTH secretion. Fed Proc 39: 2923–2930

    Google Scholar 

  • Giguere V, Cote J, Labrie F (1981) Characteristics of the alpha adrenergic cells. Endocrinology 109: 757–762

    Google Scholar 

  • Giguere V, Citoe J, Labrie F (1982) Specific inhibition by glucocorticoids of the alpha-2 adrenergic stimulation of adrenocorticotropin release in rat anterior pituitary cells. Endocrinology 110: 1225–1230

    Google Scholar 

  • Girgis SI, Galan GF, Arnett TR, Rogers RM, Bone Q, Ravazzola M, MacIntyre I (1980) Immune reactive human calcitonin in the nervous systems of protochordates and acyclostome mixine. J Endocrinol 87: 375–382

    Google Scholar 

  • Golzman D (1980) Examination of interspecies differences in renal and skeletal receptor binding and adenylate cyclase stimulation with human calcitonin. Endocrinology 106: 510–518

    Google Scholar 

  • Hermus AR, Pieters GF, Smals AG, Benrad TJ, Kloppenborg PW (1984) Plasma adrenocorticotropin, cortisol and aldosterone response to corticotropin releasing factor: modulatory effect of basal cortisol levels. J Clin Endocrinol Metab 58: 187–191

    Google Scholar 

  • Imura H, Nakay Y, Yoshini T (1973) Effect of 5-hydroxytryptophan on GH and ACTH release in man. J Clin Endocrinol Metab 36: 204–206

    Google Scholar 

  • Jackson RW, De Cherney GS, De BoldCR, Sheldon WR, Alexander AN, Rivier J (1984) Synthetic ovine corticotropin releasing hormone-simultaneous release of propiomelanocortin peptides in man. J Clin Endocrinol Metab 58: 740–743

    Google Scholar 

  • Jones MT, Hillhouse EW, Burden J (1976) Effect of various putative neurotransmitters on the secretion of CRF from the rat hypothalamus in vitro: a model of the neurotransmitters involved. J Endocrinol 69: 1–10

    Google Scholar 

  • Jones MT, Birmingham M, Gillham B, Holmes M, Smith T (1979) The effect of cyproheptadine on the release of CRF. Clin Endocrinol 10: 203–205

    Google Scholar 

  • Krieger HP, Krieger DT (1970) Chemical stimulation of the brain: effect on adrenal corticoid release. Am J Physiol 219: 1632–1641

    Google Scholar 

  • Krieger DT, Amorosa L, Linick F (1975) Cyproheptadine induced remission of Cushing's disease. N Engl J Med 293: 893–896

    Google Scholar 

  • Krieger DT, Luria M (1976) Effectiveness of cyproheptadine in decreasing plasma ACTH concentrations in Nelson's syndrome. J Clin Endocrinol Metab 43: 1179–1182

    Google Scholar 

  • Lamberts SW, Bons EG, Uitterlinden P, Hackeng WH (1983) Cyproheptadine and desmethylcyproheptadine directly inhibit the release of adrenocorticotropin and β-lipotropin/β-endorphin actively from the neurointermediate lobe of the rat pituitary gland. J Endocrinol 96: 395–400

    Google Scholar 

  • Laurian L, Oberman Z, Graf E, Gilad S, Hoerer E, Simantov R (1986) Calcitonin induced increase in ACTH, β-endorphin and cortisol secretion. Horm Metab Res 18: 268–271

    Google Scholar 

  • Lewis DA, Sherman BM (1984) Serotonergic stimulation of adrenocorticotropin secretion in man. J Clin Endocrinol Metab 58: 458–462

    Google Scholar 

  • Nakahala AM, Masundara APN (1978) Calcitonin mediated changes in plasma tryptophan and brain 5-hydroxytryptamine and acetylcholinesterase in rats. Biochem J 170: 445–452

    Google Scholar 

  • Nakanishi S, Inoue A, Kita T, Nakamura M, Chang AC, Cohen SN, Numa S (1979) Nucleotide sequences of cloned cDNA for bovine corticotropin β-lipotropin precursor. Nature 278: 423–427

    Google Scholar 

  • Naumenko EV (1968) 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 11: 1–10

    Google Scholar 

  • Petraglia F, Facchinetti F, Martignoni E, Nappi G, Volpe A, Genazzani AR (1984) Serotonergic agonists increase plasma levels of β-endorphin and β-lipotropin in human. J Clin Endocrinol Metab59: 1138–1142

    Google Scholar 

  • Plonk JW, Bivems CH, Feldman JM (1974) Inhibition of hypoglycemia induced cortisol secretion by the serotonin antagonist cyproheptadine. J Clin Endocrinol Metab 38: 836–840

    Google Scholar 

  • Scanlon MF, Smith BR, Hall R (1978) Thyrotrop stimulating hormone: neuroregulation and clinical applications. Clin Sci Mol Med 55: 129–138

    Google Scholar 

  • Stekolinikov LI, Abdokarimov A (1969) Physiochemical study of cerebrospinal fluid under thyrocalcitonin action. Biofizika 14: 921–925

    Google Scholar 

  • Stone CA, Wenger WE, Ludden CT, Stavorski JM, Ross CA (1961) Antiserotonin-anti-histaminic properties of cyproheptadine. J Pharmacol Exp Ther 131: 1–6

    Google Scholar 

  • Vale W, Rivier C, Yang L, Minick S, Guillemin R (1978) Effects of purified hypothalamic CRF and other substances on the secretion of ACTH and β-endorphin like immunoreactivities in vitro. Endocrinology 103: 1910–1915

    Google Scholar 

  • Vale W, Vaugham J, Smith M, Yamamoto G, Rivier J, Rivier C (1983) Effects of synthetic ovine corticotropin releasing factor, glucocorticoids, catecholamines, neurohypophyseal peptides and other substances on cultured corticotropic cells. Endocrinology 113: 1121–1131

    Google Scholar 

  • Winkelmann W, Allolio B, Deuss U, Schulte HM (1987) Inhibitory action of cyproheptadine on corticotropin-releasing CRH-induced hormone release. Acta Endocr (Copenh) [Suppl 283] 114: 47–48

    Google Scholar 

  • Yamaguchi H, Liotta AS, Krieger DT (1980) Simultaneous determination of human plasma immunoreactive β-lipotropin gama lipotropin and β-endorphin using immune affinity chromatography. J Clin Endocrinol Metab 51: 1002–1008

    Google Scholar 

Download references

Author information

Author notes

  1. L. Laurian

    Present address: Department of Endocrinology, Ichilov Hospital, Tel Aviv Medical Center, Tel Aviv, Israel

Authors and Affiliations

  1. Department of Endocrinology, Ichilov Hospital, Tel Aviv Medical Center, Tel Aviv, Israel

    E. Hoerer

  2. Department of Chemical Pathology, Ichilov Hospital, Tel Aviv Medical Center, Tel Aviv, Israel

    Z. Oberman & E. Graf

  3. Department of the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    L. Laurian

Authors
  1. L. Laurian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z. Oberman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Hoerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laurian, L., Oberman, Z., Hoerer, E. et al. Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin, ACTH, and cortisol secretion. J. Neural Transmission 73, 167–176 (1988). https://doi.org/10.1007/BF01250134

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01250134

Keywords

Search

Navigation