Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Regulation of Growth Hormones

Activation of the Somatotropic Axis by Testosterone in Adult Men: Evidence for a Role of Hypothalamic Growth Hormone-Releasing Hormone

Bondanelli M. · Ambrosio M.R. · Margutti A. · Franceschetti P. · Zatelli M.C. · degli Uberti E.C.

Author affiliations

Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Ferrara, Italy

Related Articles for ""

Neuroendocrinology 2003;77:380–387

Do you have an account?

Login Information





Contact Information












By signing up for MyKarger you will automatically participate in our year-End raffle.
If you Then Do Not wish To participate, please uncheck the following box.

Yes, I wish To participate In the year-End raffle And Get the chance To win some Of our most interesting books, And other attractive prizes.


I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information












By signing up for MyKarger you will automatically participate in our year-End raffle.
If you Then Do Not wish To participate, please uncheck the following box.

Yes, I wish To participate In the year-End raffle And Get the chance To win some Of our most interesting books, And other attractive prizes.


I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

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 Regulation of Growth Hormones

Received: December 06, 2002
Accepted: March 03, 2003
Published online: July 08, 2003
Issue release date: June 2003

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

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

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

Abstract

Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 ± 2.4 years (mean ± SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 ± 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 ± 0.11 µg/l) and IGF-I (23.79 ± 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 ± 0.28 µg/l; IGF-I 28.71 ± 1.46 nmol/l). The mean ΔGH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 ± 0.86 µg/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 ± 1.33 µg/l) and significantly increased after T replacement therapy (5.52 ± 1.25 µg/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E2) levels significantly correlated with ΔGH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E2 plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function.

© 2003 S. Karger AG, Basel


References

  1. Giustina A, Veldhuis JD: Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998;19:717–797.
  2. Kerrigan JR, Rogol AD: The impact of gonadal steroid hormone action on growth hormone secretion during childhood and adolescence. Endocr Rev 1992;13:281–298.
  3. Veldhuis JD, Evans WS, Shah N, Story S, Bray MJ, Anderson SM: Proposed mechanisms of sex-steroid hormone neuromodulation in the human GH-IGF-I axis; in Veldhuis JD, Giustina A (eds): Sex-Steroid Interactions with Growth Hormone. New York, Springer, 1999, pp 93–121.
  4. Link K, Blizzard RM, Evans WS, Kaiser DL, Parker MW, Rogol AD: The effect of androgens on the pulsatile release and the twenty-four-hour mean concentration of growth hormone in peripubertal males. J Clin Endocrinol Metab 1986;62:159–164.
  5. Liu L, Merriam GR, Sherins RJ: Chronic sex steroid exposure increases mean plasma growth hormone concentration and pulse amplitude in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1987;64:651–656.
  6. Ulloa-Aguirre A, Blizzard RM, Garcia-Rubi E, Rogol AD, Link K, Christie CM, Johnson ML, Veldhuis JD: Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin Endocrinol Metab 1990;71:846–854.
  7. Weissberger AJ, Ho KK: Activation of the somatotropic axis by testosterone in adult males: Evidence for the role of aromatization. J Clin Endocrinol Metab 1993;76:1407–1412.
  8. Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER: Androgen-stimulated pubertal growth: The effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab 1993;76:996–1001.
  9. Eakman GD, Dallas JS, Ponder SW, Keenan BS: The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. J Clin Endocrinol Metab 1996;81:1217–1223.
  10. Giustina A, Scalvini T, Tassi C, Desenzani P, Poiesi C, Wehrenberg WB, Rogol AD, Veldhuis JD: Maturation of the regulation of growth hormone secretion in young males with hypogonadotropic hypogonadism pharmacologically exposed to progressive increments in serum testosterone. J Clin Endocrinol Metab 1997;82:1210–1219.
  11. DiMartino-Nardi J, Wu R, Fishman K, Saenger P: The effect of long-acting analog of luteinizing hormone-releasing hormone on growth hormone secretory dynamics in children with precocious puberty. J Clin Endocrinol Metab 1991;73:902–926.
  12. Harris DA, Van Vliet G, Egli CA, Grumbach MM, Kaplan SL, Styne DM, Vainsel M: Somatomedin-C in normal puberty and in true precocious puberty before and after treatment with a potent luteinizing hormone-releasing hormone agonist. J Clin Endocrinol Metab 1985;61:152–159.
  13. Martin LG, Clark JW, Connor TB: Growth hormone secretion enhanced by androgens. J Clin Endocrinol Metab 1968;28:425–428.
  14. Gentili A, Mulligan T, Godschalk M, Clore J, Patrie J, Iranmanesh A, Veldhuis JD: Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. J Clin Endocrinol Metab 2002;87:825–834.
  15. Miki N, Ono M, Miyoshi H, Tsushima T, Shizume K: Hypothalamic growth hormone-releasing factor participates in the negative feedback regulation of growth hormone secretion. Life Sci 1989;44:469–476.
  16. Sugihara H, Minami S, Wakabayashi I: Post-somatostatin rebound secretion of growth hormone is dependent on growth hormone-releasing factor in unrestrained female rats. J Endocrinol 1989;122:583–591.
  17. Robinson IC, Jeffery S, Clark RG: Somatostatin and its physiological significance in regulating the episodic secretion of growth hormone in the rat. Acta Pediatr Scand Suppl 1990;367:87–92.
  18. Cella SG, Luceri M, Cattaneo L, Torsello A, Muller EE: Somatostatin withdrawal as generator of pulsatile GH release in the dog: A possible tool to evaluate the endogenous GHRH tone? Neuroendocrinology 1996;63:481–488.
  19. Rigamonti AE, Cavallera G, Bonomo S, Deghenghi R, Locatelli V, Cella SG, Muller EE: Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: Studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide. Eur J Endocrinol 2001;145:635–644.
  20. Hindmarsh PC, Brain CE, Robinson IC, Matthews DR, Brook CG: The interaction of growth hormone-releasing hormone and somatostatin in the generation of a GH pulse in man. Clin Endocrinol (Oxf) 1991;35:353–360.
  21. degli Uberti EC, Ambrosio MR, Cella SG, Margutti AR, Trasforini G, Rigamonti AE, Petrone E, Muller EE: Defective hypothalamic growth hormone (GH)-releasing hormone activity may contribute to declining GH secretion with age in man. J Clin Endocrinol Metab 1997;82:2885–2888.
  22. Cappa M, Rigamonti AE, Bizzarri C, Porzio O, Civolani P, Cella SG, Loche S, Muller EE: Somatostatin infusion withdrawal: Studies in normal children and in children with growth hormone deficiency. J Clin Endocrinol Metab 1999;84:4426–4430.
  23. Magnan E, Cataldi M, Guillaume V, Conte-Devolx B, Graziani N, Figaroli JC, Thomas F, Chihara K, Oliver C: Acute changes in growth hormone-releasing hormone secretion after injection of BIM 23014, a long-acting somatostatin analog, in rams. Life Sci 1992;51:831–838.
  24. Fryburg DA, Weltman A, Jahn LA, Weltman JY, Samojlik E, Hintz RL, Veldhuis JD: Androgenic modulation of the growth Hormone-IGF axis and its impact on metabolic outcomes; in Veldhuis JD, Giustina A (eds): Sex-Steroid Interaction with Growth Hormone. New York, Springer, 1999, pp 82–92.
  25. Veldhuis JD, Metzger DL, Martha PM Jr, Mauras N, Kerrigan JR, Keenan B, Rogol AD, Pincus SM: Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: Evidence from pubertal pathophysiology and sex-steroid hormone replacement. J Clin Endocrinol Metab 1997;82:3414–3420.
  26. Andersen M, Hansen TT, Stoving RK, Bertelsen J, Hangaard J, Hyltoft Petersen P: The pyridostigmine-growth-hormone-releasing hormone test in adults. The reference interval and a comparison with the insulin tolerance test. Endocrinol Metab 1996;3:197–206.
  27. Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E: Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 1998;83:1615–1618.
  28. Ghigo E, Arvat E, Aimaretti G, Broglio F, Giordano R, Camanni F: Diagnostic and therapeutic uses of growth hormone-releasing substances in adult and elderly subjects. Baillieres Clin Endocrinol Metab 1998;12:341–358.
  29. Valetto MR, Bellone J, Baffoni C, Savio P, Aimaretti G, Gianotti L: Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur J Endocrinol 1996;135:135–138.
  30. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, Bartolotta E, Dammacco F, Cammani F: Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab 1996;81:3323–3327.
  31. Brann DW: Glutamate: A major excitatory transmitter in neuroendocrine regulation. Neuroendocrinology 1995;61:213–225.
  32. Fryburg DA, Weltman A, Jahn LA, Weltman JY, Samojlik E, Hintz RL, Veldhuis JD: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol Metab 1997;82:3710–3719.
  33. Del Rio G, Carani C, Velardo A, Zizzo G, Procopio M, Coletta F, Marrama P, Ghigo E: Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism. J Endocrinol Invest 1995;18:690–695.
  34. Müller EE, Locatelli V, Cocchi D: Neuroendocrine control of growth hormone secretion. Physiol Rev 1999;79:511–607.
  35. Iranmanesh A, South S, Liem AY, Clemmons D, Thorner MO, Weltman A, Veldhuis JD: Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men. Eur J Endocrinol 1998;139:59–71.
  36. Iranmanesh A, Lizarralde G, Veldhuis JD: Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991;73:1081–1088.
  37. Plotsky PM, Vale W: Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. Science 1985;230:461–463.
  38. Frohman LA, Downs TR, Clarke IJ, Thomas GB: Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthesized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia. J Clin Invest 1990;86:17–24.
  39. Lumpkin MD, Mulroney SE, Haramati A: Inhibition of pulsatile growth hormone (GH) secretion and somatic growth in immature rats with a synthetic GH-releasing factor antagonist. Endocrinology 1989;124:1154–1159.
  40. Rizvi SS, Weinbauer GF, Arslan M, Partsch CJ, Nieschlag E: Testosterone modulates growth hormone secretion at the hypothalamic but not at the hypophyseal level in the adult male rhesus monkey. J Endocrinol 2000;165:337–344.
  41. Ho KY, Evans WS, Blizzard RM, Veldhuis JD, Merriam JR, Samojlik E, Furlanetto R, Rogol AD, Kaiser DL, Thorner MO: Effect of sex and age on the 24-hour profile of growth hormone secretion in man: Importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 1987;64:51–58.

Article / Publication Details

First-Page Preview
Abstract of Regulation of Growth Hormones

Received: December 06, 2002
Accepted: March 03, 2003
Published online: July 08, 2003
Issue release date: June 2003

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

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.