This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gianotti, L. Articles by Arvat, E. Search for Related Content PubMed PubMed Citation Articles by Gianotti, L. Articles by Arvat, E.

Arginine Counteracts the Inhibitory Effect of Recombinant Human Insulin-Like Growth Factor I on the Somatotroph Responsiveness to Growth Hormone-Releasing Hormone in Humans¹

Division of Endocrinology, Department of Internal Medicine, University of Turin, 10126 Turin, Italy; and Department of Pharmacology, University of Milan (E.E.M.), 20100 Milan, Italy

Address all correspondence and requests for reprints to: E. Ghigo, M.D., Divisione di Endocrinologia, Ospedale Molinette, Corso Dogliotti 14, 10126 Torino, Italy. E-mail: ezio.ghigo{at}unito.it

Insulin-like growth factor I (IGF-I) exerts a negative feedback effect on GH secretion via either direct actions at the pituitary level or indirect ones at the hypothalamic level, through stimulation of somatostatin (SS) and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) in humans inhibits spontaneous GH secretion as well as the GH response to GHRH and even more to GH/GH-releasing peptides, whose main action is on the hypothalamus, antagonizing SS and enhancing GHRH activity. The aim of the present study was to further clarify in humans the mechanisms underlying IGF-I-induced inhibition of somatotroph secretion. In six normal young volunteers (all women; mean ± SEM: age, 28.3 ± 1.2 yr; body mass index, 21.3 ± 1.2 kg/m²) we studied the GH response to GHRH (1 µg/kg, iv, at 0 min), both alone and combined with arginine (ARG; 0.5 g/kg, iv, from 0–30 min), which probably acts via inhibition of hypothalamic SS release, after pretreatment with rhIGF-I (20 µg/kg, sc, at -180 min) or placebo. rhIGF-I increased circulating IGF-I levels (peak at -60 vs. -180 min: 54.9 ± 3.9 vs. 35.9 ± 3.3 mmol/L; P < 0.05) to a reproducible extent, and these levels remained stable and within the normal range until 90 min. The mean GH concentration over 3 h (from -180 to 0 min) before ARG and/or GHRH was not modified by placebo or rhIGF-I. After placebo, the GH response to GHRH (peak, 23.6 ± 2.9 µg/L) was strikingly enhanced (P < 0.05) by ARG coadministration (69.6 ± 9.9 µg/L). rhIGF-I blunted the GH response to GHRH (13.1 ± 4.5 µg/L; P < 0.05), whereas that to GHRH plus ARG was not modified (59.5 ± 8.9 µg/L), although it occurred with some delay. Mean glucose and insulin concentrations were not modified by either placebo or rhIGF-I. In conclusion, ARG counteracts the inhibitory effect of rhIGF-I on somatotroph responsiveness to GHRH in humans. These findings suggest that the acute inhibitory effect of rhIGF-I on the GH response to GHRH takes place on the hypothalamus, possibly via enhancement of SS release, and that ARG overrides this action.

This article has been cited by other articles:

				J. D. Veldhuis, M. Cosma, D. Erickson, R. Paulo, K. Mielke, L. S. Farhy, and C. Y. Bowers Tripartite Control of Growth Hormone Secretion in Women during Controlled Estradiol Repletion J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2336 - 2345. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, D. Erickson, K. Mielke, L. S. Farhy, D. M. Keenan, and C. Y. Bowers Distinctive Inhibitory Mechanisms of Age and Relative Visceral Adiposity on Growth Hormone Secretion in Pre- and Postmenopausal Women Studied under a Hypogonadal Clamp J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6006 - 6013. [Abstract] [Full Text] [PDF]

				J. D Veldhuis, D. M Keenan, K. Mielke, J. M Miles, and C. Y Bowers Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy Eur. J. Endocrinol., October 1, 2005; 153(4): 577 - 586. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Iranmanesh, and C. Y. Bowers Joint Mechanisms of Impaired Growth-Hormone Pulse Renewal in Aging Men J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4177 - 4183. [Abstract] [Full Text] [PDF]

				C. Soares-Welch, L. Farhy, K. L. Mielke, F. H. Mahmud, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis Complementary Secretagogue Pairs Unmask Prominent Gender-Related Contrasts in Mechanisms of Growth Hormone Pulse Renewal in Young Adults J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2225 - 2232. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. Y. Weltman, A. L. Weltman, A. Iranmanesh, E. E. Muller, and C. Y. Bowers Age and Secretagogue Type Jointly Determine Dynamic Growth Hormone Responses to Exogenous Insulin-Like Growth Factor-Negative Feedback in Healthy Men J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5542 - 5548. [Abstract] [Full Text] [PDF]

				D. Erickson, D. M. Keenan, K. Mielke, K. Bradford, C. Y. Bowers, J. M. Miles, and J. D. Veldhuis Dual Secretagogue Drive of Burst-Like Growth Hormone Secretion in Postmenopausal Compared with Premenopausal Women Studied under an Experimental Estradiol Clamp J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4746 - 4754. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, S. M. Anderson, P. Kok, A. Iranmanesh, J. Frystyk, H. Orskov, and D. M. Keenan Estradiol Supplementation Modulates Growth Hormone (GH) Secretory-Burst Waveform and Recombinant Human Insulin-Like Growth Factor-I-Enforced Suppression of Endogenously Driven GH Release in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1312 - 1318. [Abstract] [Full Text] [PDF]

				R. Nass, S. S. Pezzoli, I. M. Chapman, J. Patrie, R. L. Hintz, M. L. Hartman, and M. O. Thorner IGF-I does not affect the net increase in GH release in response to arginine Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E702 - E710. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, M. Bidlingmaier, S. M. Anderson, Z. Wu, and C. J. Strasburger Lowering Total Plasma Insulin-Like Growth Factor I Concentrations by Way of a Novel, Potent, and Selective Growth Hormone (GH) Receptor Antagonist, Pegvisomant (B2036-Peg), Augments the Amplitude of GH Secretory Bursts and Elevates Basal/Nonpulsatile GH Release in Healthy Women and Men J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3304 - 3310. [Abstract] [Full Text] [PDF]