Horm Metab Res 2005; 37(8): 489-493
DOI: 10.1055/s-2005-870307
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Intranasal Administration of ACTH(1-24) Stimulates Catecholamine Secretion

M.  Yoshida-Hiroi1 , Y.  Tsuchida2 , G.  Yoshino2 , N.  Hiroi2, 3
  • 1 Division of Respiratory Disease, Department of Internal Medicine, Toho University School of Medicine, Japan
  • 2 Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Japan
  • 3 Department of Internal Medicine, Saiseikai Kanagawa-Ken Hospital, Japan
Further Information

Publication History

Received 24 May 2005

Accepted after revision 16 June 2005

Publication Date:
01 September 2005 (online)

Abstract

Previously, we reported that intranasal (IN) ACTH(1-24) administration stimulates adrenocortical steroid secretion in normal subjects. To determine the efficiency of transmucosal absorption of ACTH into the adrenal medulla, we measured serum cortisol, aldosterone, epinephrine, norepinephrine and dopamine levels after IN vs. intravenous (IV) administration of 250 μg ACTH(1-24) in 7 healthy adult men (mean age 21.7 ± 1.2 yr; range, 21 - 24 yr). Blood was collected at 0, 30, 60 and 120 min after administration of ACTH(1-24), and the levels of adrenocortical steroids and catecholamines were measured by specific RIA and HPLC methods, respectively. There were no side effects associated with IN or IV ACTH administration. Consistent with the previous study, serum cortisol and aldosterone increased after IN administration of ACTH(1-24), peaking 30 min after administration. Sixty minutes after IN and IV administration of ACTH, epinephrine levels increased by 41.9 ± 13.1 % and 63.3 ± 11.8 %, respectively, and remained elevated throughout the sampling period. Thirty minutes after IN or IV administration of ACTH(1-24), plasma norepinephrine levels increased by 55.9 ± 13.4 % and 73.7 ± 15.0 %, respectively, peaking 30 min after ACTH(1-24) administration, and decreasing to basal levels within 60 min. Plasma dopamine levels did not change after IN administration of ACTH(1-24). Adrenocortical steroid and catecholamine levels did not increase after IN administration of saline. These results demonstrate that IN administration of ACTH(1-24) not only stimulates adrenocortical steroids, but also epinephrine and norepinephrine.

References

  • 1 Axelrod J. Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines.  Pharmacol Rev. 1966;  18 95-113
  • 2 Hiroi N, Ichijo T, Ueshiba H, Miyachi Y. Intranasal administration of adrenocorticotropin-(1-24) stimulates adrenocortical hormone secretion.  J Clin Endocrinol Metab. 2002;  87 1750-1753
  • 3 Yoshida-Hiroi M, Bradbury M J, Eisenhofer G, Hiroi N, Vale W W, Novotny G E, Hartwig H G, Scherbaum W A, Bornstein S R. Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice.  Mol Psychiatry. 2002;  7 967-974
  • 4 Nohta H, Lee M K, Ohkura Y. Fluorescence products of the reaction for the determination of catecholamines with 1,2-diarylethylenediamines.  Analytica Chimica Acta. 1992;  267 137-139
  • 5 Rudman D, Moffitt S D, Fernhoff P M, Blackston R D, Faraj B A. Epinephrine deficiency in hypocorticotropic hypopituitary children.  J Clin Endocrinol Metab. 1981;  53 722-729
  • 6 Bornstein S R, Tajima T, Eisenhofer G, Haidan A, Aguilera G. Adrenomedullary function is severely impaired in 21-hydroxylase-deficient mice.  FASEB J. 1999;  13 1185-1194
  • 7 Merke D P, Chrousos G P, Eisenhofer G, Weise M, Keil M F, Rogol A D, Van Wyk J J, Bornstein S R. Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency.  N Engl J Med. 2000;  343 1362-1368
  • 8 Wurtman R J. Control of epinephrine synthesis by the pituitary and adrenal cortex: possible role in the pathophysiology of chronic stress.  Recent Adv Biol Psychiatry. 1966;  9 359-368
  • 9 Axelrod J, Reisine T D. Stress hormones: their interaction and regulation.  Science. 1984;  224 452-459
  • 10 Doupe A J, Landis S C, Patterson P H. Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity.  J Neurosci. 1985;  5 2119-2142
  • 11 Wurtman R J, Axelrod J. Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids.  J Biol Chem. 1966;  241 2301-2305
  • 12 Ray P P, Chaudhuri-Sengupta S, Maiti B R. Adrenomedullary and glycemic responses to ACTH, corticosterone, aldosterone, epinephrine and norepinephrine administrations in the soft-shelled turtle.  Folia Biol (Krakow). 2004;  52 73-80
  • 13 Mountjoy K G, Robbins L S, Mortrud M T, Cone R D. The cloning of a family of genes that encode the melanocortin receptors.  Science. 1992;  257 1248-1251
  • 14 Liakos P, Chambaz E M, Feige J J, Defaye G. Expression and regulation of melanocortin receptor-5 (MC5-R) in the bovine adrenal cortex.  Mol Cell Endocrinol. 2000;  159 99-107
  • 15 Bornstein S R, Ehrhart-Bornstein M, Usadel H, Bockmann M, Scherbaum W A. Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland.  Cell Tissue Res. 1991;  265 1-9
  • 16 Bornstein S R, Gonzalez-Hernandez J A, Ehrhart-Bornstein M, Adler G, Scherbaum W A. Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions.  J Clin Endocrinol Metab. 1994;  78 225-232
  • 17 Bornstein S R, Ehrhart-Bornstein M. Ultrastructural evidence for a paracrine regulation of the rat adrenal cortex mediated by the local release of catecholamines from chromaffin cells.  Endocrinology. 1992;  131 3126-3168
  • 18 Hansen I L, Levy M M, Kerr D S. Differential diagnosis of hypoglycemia in children by responses to fasting and 2-deoxyglucose.  Metabolism. 1983;  32 960-970
  • 19 Sizonenko P C, Paunier L, Vallotton B, Cuendet G S, Zahnd G, Marliss E B. Response to 2-deoxy-D-glucose and to glucagon in “ketotic hypoglycemia” of childhood: evidence for epinephrine deficiency and altered alanine availability.  Pediatr Res. 1973;  7 983-993
  • 20 Kjaer M. Regulation of hormonal and metabolic responses during exercise in humans.  Exerc Sport Sci Rev. 1992;  20 161-184
  • 21 Johnson M D, Grignolo A, Kuhn C M, Schanberg S M. Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats.  Life Sci. 1983;  33 169-180
  • 22 Siltanen P. Stress, coronary disease, and coronary death.  Ann Clin Res. 1987;  19 96-103
  • 23 Hauss W H, Bauch H J, Schulte H. Adrenaline and noradrenaline as possible chemical mediators in the pathogenesis of arteriosclerosis.  Ann N Y Acad Sci. 1990;  598 91-101
  • 24 Southwick S M, Paige S, Morgan C A , Bremner J D, Krystal J H, Charney D S. Neurotransmitter alterations in PTSD: catecholamines and serotonin.  Semin Clin Neuropsychiatry. 1999;  4 242-248
  • 25 Swerdlow A J, Higgins C D, Brook C G, Dunger D B, Hindmarsh P C, Price D A, Savage M O. Mortality in patients with congenital adrenal hyperplasia: a cohort study.  J Pediatr. 1998;  133 516-520
  • 26 Hinde F R, Johnston D I. Hypoglycaemia during illness in children with congenital adrenal hyperplasia.  Br Med J (Clin Res Ed). 1984;  289 1603-1604
  • 27 Weise M, Mehlinger S L, Drinkard B, Rawson E, Charmandari E, Hiroi M, Eisenhofer G, Yanovski J A, Chrousos G P, Merke D P. Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise.  J Clin Endocrinol Metab. 2004;  89 591-597
  • 28 Lalej-Bennis D, Boillot J, Bardin C, Zirinis P, Coste A, Escudier E, Chast F, Peynegre R, Slama G, Selam J L. Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance.  Diabetes Metab. 2001;  27 372-377
  • 29 Wilson A M, Sims E J, Lipworth B J. Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment.  Clin Endocrinol (Oxf). 1999;  50 329-335
  • 30 Lipworth B J. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.  Arch Intern Med. 1999;  159 941-955
  • 31 Casale T B, Nelson H S, Stricker W E, Raff H, Newman K B. Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.  Ann Allergy Asthma Immunol. 2001;  87 379-385

Naoki Hiroi, M. D., Ph. D.

Department of Internal Medicine, Saiseikai Kanagawa-Ken Hospital

6-6 Tomiyacho · Kanagawa-ku · Yokohama · Kanagawa 221-8601 · Japan

Phone: +81 (45) 432-1111

Fax: +81 (45) 432-1119 ·

Email: n-hiroi@tkf.att.ne.jp