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PLASMA steroid responses to circadian-stage-specified injection of different doses of the acth analogue alsactide (ACTH 1–17) in healthy adult human males

  • Franco Veglio
  • Marilena Padoan
  • Margherita Gambino
  • Piero Paccotti
  • Massimo Terzolo
  • Alberto Angeli
Original Contributions

Summary

Plasma cortisol, progesterone, testosterone and aldosterone levels were measured on serial blood samples drawn in 10 healthy adult human males up to 6h after single administration at about 0715 of increasing amounts of the short-chain analogue ACTH-agonist alsactide (Synchro-dyn® 1–17). The following doses were employed: 2, 4, 8, 10 and 20 μg subcutaneously (s.c.), as well as 2, 4 and 8 μg intravenously (i.v.). Data were compared with those obtained by placebo (isotonic saline) injections. The s.c. injections of 2 and 4 μg resulted to be ineffective in changing the hormonal pattern. A significant rise of cortisol and progesterone, but not of aldosterone and testosterone, followed the s.c. injections of 8 and 10 μg. The differential pattern of the glucocorticoidvs. the mineralocorticoid response was also apparent after the s.c. injection of 20 μg alsactide; when compared with placebo, this dose was able to elicit a significant increase of all examined hormones except testosterone. All i.v. injections of 2, 4 and 8 μg alsactide were effective; the highest dose did cause a sustained rise of plasma cortisol, progesterone and aldosterone, but also the other doses were able to change significantly the mineralocorticoid levels. These results provide evidence that circadian-stage-specified s.c. or i.v. administration of the analogue can be employed in the clinical practice for enhancing selectively and transiently the morning glucocorticoid secretion.

Key-words

ACTH 1–17 Alsactide Analogue Circadian stage Steroid hormones 

References

  1. 1.
    Angeli A.: Glucocorticoid secretion: a circadian synchronizer of the human temporal structure - J. Steroid Biochem.19, 545, 1983.PubMedCrossRefGoogle Scholar
  2. 2.
    Angeli A., Carandente E., Dammacco E., Martini L.: Progress in chronophysiology of peptide hormones with emphasis on clinical application of analogues - Chronobiologia12, 293, 1985.PubMedGoogle Scholar
  3. 3.
    Angeli A., Gatti G., Cavallo R., Cartgnola R.: Chrononeuroendocrinology of the hypotha- lamo-pituitary-adrenal system and testicular function. In:Pancheri P., Zichella A. (Eds): Biorhythms and stress in the pathophysiology of reproduction. Hemisphere Publ. Co., New York, 1988. (In press).Google Scholar
  4. 4.
    Angeli A., Paccotti P., Orlandi E., Gaidano G., Cersa F.: Differential patterns of plasma cortisol and aldosterone following stimulation with increasing doses of the synthetic analogue (β-Ala1, Lys17) ACTH 1-17-4-amino-N-butylamide - Hormone metabol. Res.13, 24, 1981.Google Scholar
  5. 5.
    Bartter E. C., Delea C. S., Halberg F.: A map of blood and urinary changes related to circadian variations in adrenal corticoid function in normal subjects - Ann. N.Y. Acad. Sci.98, 969, 1962.PubMedGoogle Scholar
  6. 6.
    Battelli T., Mattio H.R., Manoccm P., Giustini L., Ginnetti A., Burattini L.: ACTH 1-17 effects in oncology - La Ricerca Clin. Lab.14, 205, 1984.Google Scholar
  7. 7.
    Brown H., Halberg E., Haus E., Lagatua D., Bere H., Sackett T., Melby J., Wilson T.: Circadian-stage-specified effects of a synthetic short chain ACTH-I-17 (HOE 433) on blood leukocytes and corticosterone secretion in mice - Chronobiologia7, 21, 1980.PubMedGoogle Scholar
  8. 8.
    Bureau J.R., Garrelly L., Coupè M., Labrecque G.: Circadian rhythm studies on BCG-in- duced migration of PMN in normal and adrenalectomized mice - Ann. Rev. Chronopharma- col.1, 333, 1984.Google Scholar
  9. 9.
    Carandente F.: Heptadecapeptide ACTH 1-17: the first analogue in chronobiology - La Ricerca Clin. Lab.14, 111, 1984.Google Scholar
  10. 10.
    Ceresa F., Angeli A., Boccuzzi G., Bisbocr D., Frairia R.: Caratteristiche della risposta cortisolemica iniziale dopo stimolazione endovenosa impulsiva con corticotropina sintetica β 1-24 - Boll. Soc. ital. Biol. sper.47, 122, 1971.Google Scholar
  11. 11.
    Ceresa E, Paccotti R, Orlandi F., Tabasso R., Angeli A.: Evaluation d’une nouvelle corticotrophine de synthèse: (β-Ala1,Lys17) ACTH 1-17-4-amino-N-butylamide - Ann. Endocrinol. (Paris)41, 54c, 1980.Google Scholar
  12. 12.
    Dallman M. E., Engeland W. C., Rose J. C., Wilkinson C. W., Shinsako J., Siedenburg F.: Nycthemeral rhythm in adrenal responsiveness to ACTH - Amer. J. Physiol.235, R210, 1978.PubMedGoogle Scholar
  13. 13.
    Daly J. R., Evans J. I.: Daily rhythms of steroid and associated pituitary hormones in man and their relationship to sleep - Advanc. Steroid Biochem. Pharmacol.4, 61, 1974.Google Scholar
  14. 14.
    Dammacco E., Campobasso N., Altomare E., Iodice G.: Analogues in immunology -La Ricerca Clin. Lab.14, 137, 1984.Google Scholar
  15. 15.
    Duran E., Torres J., Charro A., Oriol Bosch A.: The plasmatic 11-hydroxycorticosteroid response in the human to a synthetic octadecapeptide corticotropin (C-41795 Ba) - Hormone metabol. Res.7, 499, 1975.Google Scholar
  16. 16.
    Ferrari E., Bossolo P. A., Carnevale Schianca G. P., Solerte S. B., Fioravanti M., Nascim- bene M.: Adrenocortical responsiveness to the synthetic ACTH 1-17 analogue given at different circadian stages - Chronobiologia9, 133, 1982.PubMedGoogle Scholar
  17. 17.
    Geiger R., Schröder H. G.: New short-chain corticotrophin analogues with high corticotrophic activity. In:Lande S. (Ed.): Progress in peptide research. Gordon and Breach, New York- London-Paris, 1972; vol. 2, p. 273.Google Scholar
  18. 18.
    Halberg F.: Some physiological and clinical aspects of 24-hour periodicity - J. Lancet (USA)73, 20, 1953.Google Scholar
  19. 19.
    Halberg E., Halberg E., Herold M., Vecsei P., Gönther R., Reinberg A.: Toward a clinospec- trometry of conventional and novel effects of ACTH 1-17 Synchrodyn® in rodents and human beings. In:Takahashi R., Halberg E., Walker C. (Eds): Toward chronopharmacology. Proc. of the 8th IUPHAR Congress and Satellite Symposia, Nagasaki, July 27-28, 1981. Pergamon Press, Oxford and New York, 1982; p. 119.Google Scholar
  20. 20.
    Hrushesky W. W. M.: The clinical application of chronobiology to oncology - Amer. J. Anat.168, 519, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Keenan J., Thompson J. B., Chamberlain M. A., Besser G. M.: Prolonged corticotrophic action of a synthetic substituted 1-18 ACTH - Brit. med. J.,ii, 742, 1971.Google Scholar
  22. 22.
    Landon J., James V. H. T., Wharton M. J., Friedman M.: Threshold adrenocortical sensitivity in man and its possible application to corticotrophin bioassay - Lancetii, 697, 1967.CrossRefGoogle Scholar
  23. 23.
    Lejeune-Lenain C., van Cauter E., Desir D., Beyloos M., Franckson J.R.M.: Control of circadian and episodic variations of adrenal androgen secretion in man -J. endocrinol. Invest.10, 267, 1987.PubMedGoogle Scholar
  24. 24.
    Marrama P., Carani C., Celani M. E, Baraghini G. E, Cavani D., Montanini V.: ACTH 1-17 effects in psychogenic impotence - La Ricerca Clin. Lab.14, 233, 1984.Google Scholar
  25. 25.
    Minors D. S., Waterhouse J. M.: The kidney and hormones affecting it. In: Circadian rhythms and the human. John Wright and Sons, Bristol-London-Boston, 1981; p. 68.Google Scholar
  26. 26.
    Piazza E., Cattaneo M. T., Colombo E., Libretti A.: ACTH analogue application to oncostatic chemotherapy. A double blind approach - La Ricerca Clin. Lab.14, 257, 1984.Google Scholar
  27. 27.
    Reinberg A., Dupont W., Touitou Y., Lagoguey M., Bourgeois P., Touitou C., Muriaux G., Przyrowsky D., Guillemant S., Guillemant J., Brière L., Zeau B.: Clinical chronopbarmacology of ACTH 1-17 (Synchrodyn® 1-17). II. Effects on plasma testosterone, plasma aldosterone, plasma and urinary electrolytes (K, Na, Ca and Mg) - Chronobiologia8, 11, 1981.PubMedGoogle Scholar
  28. 28.
    Rivarola M. A., Saez J. M., Meyer H. E., Migeon C.: Metabolic clearance rate and blood production rate of testosterone and androst-4-ene-3,17-dione under basal conditions, ACTH and HCG stimulation -J. clin. Endocrinol.26, 1208, 1966.Google Scholar
  29. 29.
    Sandow J., Geiger R., Vogel H. G.: Pharmacological effects of a short chain ACTH analogue -Naunyn-Schmiedeberg’s Arch. exp. Pathol. Pharmakol.297 (Suppl. 2), R41, 1977.Google Scholar
  30. 30.
    Scheving L. E., Tsai T. H., Pauly J.E.: Chronotoxicology and chronopharmacology with emphasis on carcinostatic agents - Ann. Rev. Chronopharmacol.2, 177, 1986.Google Scholar
  31. 31.
    Sorcini G., Sciarra E., Concolino G., Rascio L.: Effect of ACTH on plasma testosterone in normal human subjects - Folia endocrinol. (Roma)16, 449, 1983.Google Scholar
  32. 32.
    Ungar E, Halberg F.: Circadian rhythm of thein vitro response of mouse adrenal to adrenocorticotropic hormone - Science137, 1058, 1962.PubMedCrossRefGoogle Scholar
  33. 33.
    Vierhapper H., Waldhäus L. W.: Comparison of the corficotropic action of two synthetic, substituted analogues of ACTH: ACTH 1-17 and ACTH 1-18 - J. clin. Endocrinol.47, 208, 1978.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Franco Veglio
    • 1
  • Marilena Padoan
    • 1
  • Margherita Gambino
    • 1
  • Piero Paccotti
    • 1
  • Massimo Terzolo
    • 1
  • Alberto Angeli
    • 1
  1. 1.Dipartimento di Biomedicina, Cattedra di Patologia Speciale MedicaUniversitgz degli Studi di TorinoOrbassano (TO)Italia

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