Neuroendocrinology

Corticotropin-Releasing Hormone and Opiate Peptides

Effect of Antalarmin, a Novel Corticotropin-Releasing Hormone Antagonist, on the Dynamic Function of the Preterm Ovine Fetal Hypothalamo-Pituitary-Adrenal Axis

Young I.R.a · Chan E.C.b · Smith R.b · Chrousos G.P.c · Veldhuis J.D.d · Canny B.J.a

Author affiliations

aDepartment of Physiology, Monash University, Clayton, Vic., and bMothers and Babies Research Centre, John Hunter Hospital, Newcastle, N.S.W., Australia; cPediatric and Reproductive Endocrinology Branch, NICHD, NIH Bethesda, Md., and dEndocrinology & Metabolism, Internal Medicine, University of Virginia, Charlottesville, Va., USA

Keywords: CorticotropinCorticotropin-releasing hormoneAdrenal steroidsFetal neuroendocrinologyOvine

Related Articles for ""
Neuroendocrinology 2002;76:47–54
https://doi.org/10.1159/000063683

Log in to MyKarger to check if you already have access to this content.




Forgot your password
Sign up to MyKarger

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates

Select
* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Corticotropin-Releasing Hormone and Opiate Peptides

Published online: July 01, 2002
Issue release date: July 2002

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

This study describes the effect of antalarmin on basal and stimulated activity of the hypothalamo-pituitary-adrenal (HPA) axis function in the late gestation ovine fetus. Fetuses received antalarmin (15 mg/h i.v.) or vehicle (cremophor El 50% in ethanol) from day 130 gestational age. Antalarmin infusion did not significantly affect immunoreactive corticotropin (ir-ACTH) concentrations, although there was a tendency for ir-ACTH to be lower and cortisol concentrations were lower in the antalarmin-treated fetuses (p < 0.01). The ir-ACTH response to corticotropin-releasing hormone (CRH) challenge was attenuated (p < 0.05) in the antalarmin-treated fetuses, but neither antalarmin- nor vehicle-treated fetuses had significant cortisol responses to CRH. The ir-ACTH response to hypoxia was diminished (p < 0.05) in the antalarmin-treated fetuses while the cortisol responses of antalarmin- and vehicle-treated fetuses were indistinguishable. Deconvolution analysis revealed no effect of antalarmin treatment on ir-ACTH secretory dynamics. In contrast, antalarmin decreased (p < 0.05) basal, mean and integrated cortisol. The plasma cortisol responses of antalarmin- and vehicle-treated fetuses to exogenous ACTH1–24 were indistinguishable. These data indicate that, while antalarmin inhibits CRH- and stress-induced ir-ACTH secretion, basal ir-ACTH secretion may be less affected by antalarmin treatment. Paradoxically, cortisol secretion is impaired by antalarmin infusion, although adrenal responsiveness to ACTH is not impaired. These results confirm a role for CRH in stress-induced ACTH secretion in the ovine fetus, though its role in the regulation of basal ACTH and cortisol secretion is unclear.

© 2002 S. Karger AG, Basel



Related Articles:

References

  1. Muglia L, Jacobson L, Dikkes P, Majzoub JA: Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature 1995;373:427–432.
    External Resources
  2. Uno H, Lohmiller L, Thieme C, Kemnitz JW, Engle MJ, Roecker EB, Farrell PM: Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus. Brain Res Dev Brain Res 1990;53:157–167.
    External Resources
  3. Sapolsky RM, Uno H, Rebert CS, Finch CE: Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 1990;10:2897–2902.
    External Resources
  4. McEwen BS, Magarinos AM: Stress effects on morphology and function of the hippocampus. Ann NY Acad Sci 1997;821:271–284.
    External Resources
  5. Meaney MJ, Diorio J, Francis D, Widdowson J, LaPlante P, Caldji C, Sharma S, Seckl JR, Plotsky PM: Early environmental regulation of forebrain glucocorticoid receptor gene expression: Implications for adrenocortical responses to stress. Dev Neurosci 1996;18:49–72.
    External Resources
  6. Weinstock M, Matlina E, Maor GI, Rosen H, McEwen BS: Prenatal stress selective alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat. Brain Res 1992;595:195–200.
    External Resources
  7. Weinstock M: Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? Neurosci Biobehav Rev 1997;21:1–10.
    External Resources
  8. Dodic M, May CN, Wintour EM, Coghlan JP: An early prenatal exposure to excess glucocorticoid leads to hypertensive offspring in sheep. Clin Sci (Colch) 1998;94:149–155.
    External Resources
  9. Phillips DI, Barker DJ, Fall CH, Seckl JR, Whorwood CB, Wood PJ, Walker BR: Elevated plasma cortisol concentrations: A link between low birth weight and the insulin resistance syndrome? J Clin Endocrinol Metab 1998;83:757–760.
    External Resources
  10. Jones CT, Roebuck MM: ACTH peptides and the development of the fetal adrenal. J Steroid Biochem 1980;12:77–82.
    External Resources
  11. Hollingworth SA, Deayton JM, Young IR, Thorburn GD: Prostaglandin E2 administered to fetal sheep increases the plasma concentrations of adrenocorticotropin (ACTH) and the proportion of ACTH in low molecular weight forms. Endocrinology 1995;136:1233–1240.
    External Resources
  12. Thorburn GD, Liggins GC: Role of the fetal pituitary-adrenal axis and placenta in the initiation of parturition; in Lamming GE (ed): Marshall’s Physiology of Reproduction. London, Chapman & Hall, 1994, vol 4, pp 1003–1036.
  13. Poore KR, Young IR, Canny BJ, Thorburn GD: Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus. J Endocrinol 1998;158:161–171.
    External Resources
  14. Poore KR, Canny BJ, Young IR: Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion. J Neuroendocrinol 1999;11:343–349.
    External Resources
  15. Canny BJ, Young IR, Veldhuis JD: Hypothalamo-pituitary disconnection of the late-gestation ovine fetus results in profound changes in cortisol secretion that are not reflected in commensurate changes in adrenocorticotropin secretion. Endocrinology 1998;139:3210–3219.
    External Resources
  16. Bassett JM, Thorburn GD: Foetal plasma corticosteroids and the initiation of parturition in sheep. J Endocrinol 1969;44:285–286.
    External Resources
  17. Thorburn GD: A time to be born. Semin Reprod Endocrinol 1994;12:213–226.
  18. Thorburn GD: The placenta, PGE2 and parturition. Early Hum Dev 1992;29:63–73.
    External Resources
  19. Antolovich GC, Ingram C, McMillen IC, Perry RA, Robinson PM, Silver M: The effect of disconnection of the pituitary from the hypothalamus in the fetal lamb upon adrenal function and gestation length. J Physiol 1989;417:152P.
  20. Antolovich GC, McMillen IC, Robinson PM, Silver M, Young IR, Perry RA: The effect of hypothalamo-pituitary disconnection on the functional and morphologic development of the pituitary-adrenal axis in the fetal sheep in the last third of gestation. Neuroendocrinology 1991;54:254–261.
    External Resources
  21. Ozolins IZ, Young IR, McMillen IC: Surgical disconnection of the hypothalamus from the fetal pituitary abolishes the corticotrophic response to intrauterine hypoglycemia or hypoxemia in the sheep during late gestation. Endocrinology 1992;130:2438–2445.
    External Resources
  22. Norman LJ, Challis JRG: Synergism between systemic corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin release in vivo varies as a function of gestational age. Endocrinology 1987;120:1052–1058.
    External Resources
  23. Carr GA, Jacobs RA, Young IR, Schwartz J, White A, Crosby S, Thorburn GD: Development of adrenocorticotropin-(1–39) and precursor peptide secretory responses in the fetal sheep during the last third of gestation. Endocrinology 1995;136:5020–5027.
    External Resources
  24. Schwartz J, Rose JC: Development of the pituitary adrenal axis in fetal sheep twins. Am J Physiol 1998;274:R1–R8.
    External Resources
  25. Chen C, Dagnino R Jr, De Souza EB, Grigoriadis DE, Huang CQ, Kim KI, Liu Z, Moran T, Webb TR, Whitten JP, Xie YF, McCarthy JR: Design and synthesis of a series of non-peptide high-affinity human corticotropin-releasing factor 1 receptor antagonists. J Med Chem 1996;39:4358–4360.
    External Resources
  26. Webster EL, Lewis DB, Torpy DJ, Zachman EK, Rice KC, Chrousos GP: In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: Suppression of pituitary ACTH release and peripheral inflammation. Endocrinology 1996;137:5747–5750.
    External Resources
  27. Veldhuis JD, Carlson ML, Johnson ML: The pituitary gland secretes in bursts: Appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations. Proc Natl Acad Sci USA 1987;84:7686–7690.
    External Resources
  28. Bocking AD, McMillen IC, Harding R, Thorburn GD: Effect of reduced uterine blood flow on fetal and maternal cortisol. J Dev Physiol 1986;8:237–245.
    External Resources
  29. Bornstein SR, Webster EL, Torpy DJ, Richman SJ, Mitsiades N, Igel M, Lewis DB, Rice KC, Joost HG, Tsokos M, Chrousos GP: Chronic effects of a nonpeptide corticotropin-releasing hormone type 1 receptor antagonist on pituitary-adrenal function, body weight and metabolic regulation. Endocrinology 1998;139:1546–1555.
    External Resources
  30. Brooks AN, Challis JRG, Norman LJ: Pituitary and adrenal responses to pulsatile ovine corticotropin-releasing factor administered to fetal sheep. Endocrinology 1987;120:2383–2388.
    External Resources
  31. Young IR, Loose JM, Kleftogiannis F, Canny BJ: Prostaglandin E2 acts via the hypothalamus to stimulate ACTH secretion in the fetal sheep. J Neuroendocrinol 1996;8:713–720.
    External Resources
  32. Ozolins IZ, Young IR, McMillen IC: Effect of cortisol infusion on basal and corticotropin-releasing factor-stimulated plasma ACTH concentrations in the sheep fetus after surgical isolation of the pituitary. Endocrinology 1990;127:1833–1840.
    External Resources
  33. Chan EC, Falconer J, Madsen G, Rice KC, Webster EL, Chrousos GP, Smith R: A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep. Endocrinology 1998;139:3357–3360.
    External Resources
  34. Castro MI, Valego NK, Zehnder TJ, Rose JC: The ratio of plasma bioactive to immunoreactive ACTH-like activity increases with gestational age in the fetal lamb. J Dev Physiol 1992;18:193–201.
    External Resources
  35. Castro MI, Valego NK, Zehnder TJ, Rose JC: Bioactive-to-immunoreactive ACTH activity changes with severity of stress in late-gestation ovine fetus. Am J Physiol 1993;265:E68–E73.
    External Resources
  36. Phillips ID, Fielke SL, Young IR, McMillen IC: The relative roles of the hypothalamus and cortisol in the control of prolactin gene expression in the anterior pituitary of the sheep fetus. J Neuroendocrinol 1996;8:929–933.
    External Resources
  37. Roebuck MM, Jones CT, Holland D, Silman R: In vitro effects of high molecular weight forms of ACTH on the fetal sheep adrenal. Nature 1980;284:616–618.
    External Resources
  38. Deayton JM, Young IR, Hollingworth SA, White A, Crosby SR, Thorburn GD: Effect of late hypothalamo-pituitary disconnection on the development of the HPA axis in the ovine fetus and the initiation of parturition. J Neuroendocrinol 1994;6:25–31.
    External Resources
  39. Ross JT, Phillips ID, Owens JA, McMillen IC: Cortisol differentially regulates pituitary-adrenal function in the sheep fetus after disconnection of the hypothalamus and pituitary. J Neuroendocrinol 1997;9:663–668.
    External Resources
  40. Fora MA, Valego NK, Lively MO, Castro MI, Rose JC: ACTH-like bioactivity and immunoactivity in fetal lamb pituitaries at 0.65 and 0.95 gestation. Reprod Fertil Dev 1996;8:195–201.
    External Resources
  41. Schwartz J, Kleftogiannis F, Jacobs RA, Thorburn GD, Crosby SR, White A: Biological activity of adrenocorticotropic hormone precursors on ovine adrenal cells. Am J Physiol 1995;268:E623–E629.
    External Resources
  42. Cudd TA, Wood CE: Prostaglandin E2 releases ovine fetal ACTH from a site not perfused by the carotid vasculature. Am J Physiol 1992;263:R136–R140.
    External Resources
  43. Cudd TA, Castro MI, Wood CE: Content, in vivo release, and bioactivity of fetal pulmonary immunoreactive adrenocorticotropin. Am J Physiol 1993;265:E667–E672.
    External Resources
  44. Phillips ID, Ross JT, Owens JA, Young IR, McMillen IC: The peptide ACTH(1–39), adrenal growth and steroidogenesis in the sheep fetus after disconnection of the hypothalamus and pituitary. J Physiol (Lond) 1996;491:871–879.
    External Resources
  45. Brooks AN, Currie IS, Gibson F, Thomas GB: Neuroendocrine regulation of sheep fetuses. J Reprod Fertil suppl 1992;45:69–84.
    External Resources
  46. Schwartz J, Gibson S, White A: Regulation of ACTH secretory pathway in cultured pituitary cells. Am J Physiol 1991;261:C793–C798.
    External Resources
  47. Schwartz J, Ash P, Ford V, Raff H, Crosby S, White A: Secretion of adrenocorticotrophin (ACTH) and ACTH precursors in ovine anterior pituitary cells: Actions of corticotrophin-releasing hormone, arginine vasopressin and glucocorticoids. J Endocrinol 1994;140:189–195.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Corticotropin-Releasing Hormone and Opiate Peptides

Published online: July 01, 2002
Issue release date: July 2002

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

2002, Vol.76, No. 1

July 2002

Article

Recommend This
TOP