Endocrinology, Vol 130, 780-788, Copyright © 1992 by Endocrine Society

ARTICLES

Time course and mechanism of growth hormone's negative feedback effect on its own spontaneous release

R Lanzi and GS Tannenbaum
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

Endogenous pulsatile GH secretion is blunted by the administration of exogenous GH; however, few data are available on the time course of GH negative feedback, and the mechanism by which this occurs still remains unclear. In the present study, we examined the temporal pattern of the inhibitory effect induced by an acute (single) and chronic (5 days) sc recombinant human (rh) GH injection regimen on spontaneous GH release in the rat and assessed the possible involvement of the hypothalamic GH- inhibitory peptide, somatostatin (SRIF), in this response. Eight-hour (0800-1600 h) GH secretory profiles, obtained from free-moving adult male rats administered a single sc injection of 200 micrograms rhGH at 0800 h, revealed a marked suppression of spontaneous GH pulses (GH peak amplitude: 45.7 +/- 10.9 vs. 207.8 +/- 31.7 ng/ml in H2O-injected control rats; P less than 0.001) lasting for up to 4.1 +/- 0.1 h after the injection (mean 4-h plasma GH level: 13.6 +/- 3.6 vs. 49.4 +/- 7.0 ng/ml in H2O-injected controls; P less than 0.01). During the subsequent 4- to 8-h period, recovery of spontaneous GH secretory bursts was evident, and neither the GH peak amplitude nor mean 4-h plasma GH level of rhGH-treated rats was significantly different from that of H2O-injected controls. The magnitude, time course, and recovery of the rhGH-induced inhibitory effect on pulsatile GH release after chronic rhGH treatment was similar to that after a single injection. Passive immunization of rhGH-treated rats with SRIF antiserum reversed the rhGH-induced inhibition of spontaneous GH pulses (peak amplitude: 131.7 +/- 53.7 vs. 7.1 +/- 3.4 ng/ml in rhGH-treated control rats given normal sheep serum; P less than 0.05) and restored both the GH peak amplitude and mean plasma GH level to values similar to those in H2O- injected controls. Taken together, these results demonstrate that: 1) the inhibitory effect of rhGH on endogenous pulsatile GH release is of short duration (approximately 4 h); 2) the time course of this response does not change after 5-day repeated rhGH administration; and 3) the feedback effect of GH on its own spontaneous release is exerted, at least in part, by increasing hypothalamic SRIF secretion. Such a mechanism of GH feedback may be important in the physiological control of pulsatile GH secretion.

This article has been cited by other articles:

				J. D. Veldhuis, D. M. Keenan, and S. M. Pincus Motivations and Methods for Analyzing Pulsatile Hormone Secretion Endocr. Rev., December 1, 2008; 29(7): 823 - 864. [Abstract] [Full Text] [PDF]

				K. Stokes, M. Nevill, J. Frystyk, H. Lakomy, and G. Hall Human growth hormone responses to repeated bouts of sprint exercise with different recovery periods between bouts J Appl Physiol, October 1, 2005; 99(4): 1254 - 1261. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. Patrie, L. Wideman, M. Patterson, J. Y. Weltman, and A. Weltman Contrasting Negative-Feedback Control of Endogenously Driven and Exercise-Stimulated Pulsatile Growth Hormone Secretion in Women and Men J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 840 - 846. [Abstract] [Full Text] [PDF]

				L. S. Farhy, M. Straume, M. L. Johnson, B. Kovatchev, and J. D. Veldhuis Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory dynamics Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R753 - R764. [Abstract] [Full Text] [PDF]

				K. A. Stokes, M. E. Nevill, G. M. Hall, and H. K. A. Lakomy Growth hormone responses to repeated maximal cycle ergometer exercise at different pedaling rates J Appl Physiol, February 1, 2002; 92(2): 602 - 608. [Abstract] [Full Text] [PDF]

				L. S. Farhy, M. Straume, M. L. Johnson, B. Kovatchev, and J. D. Veldhuis A construct of interactive feedback control of the GH axis in the male Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R38 - R51. [Abstract] [Full Text] [PDF]

				J. A. Kanaley, J. Y. Weltman, K. S. Pieper, A. Weltman, and M. L. Hartman Cortisol and Growth Hormone Responses to Exercise at Different Times of Day J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2881 - 2889. [Abstract] [Full Text] [PDF]

				D. L. Waters, C. R. Qualls, R. Dorin, J. D. Veldhuis, and R. N. Baumgartner Increased Pulsatility, Process Irregularity, and Nocturnal Trough Concentrations of Growth Hormone in Amenorrheic Compared to Eumenorrheic Athletes J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1013 - 1019. [Abstract] [Full Text]

				S. Park, J. Kamegai, T. A. Johnson, L. A. Frohman, and R. D. Kineman Modulation of Pituitary Somatostatin Receptor Subtype (sst1-5) Messenger Ribonucleic Acid Levels by Changes in the Growth Hormone Axis Endocrinology, October 1, 2000; 141(10): 3556 - 3563. [Abstract] [Full Text] [PDF]

				K. Spiegel, R. Leproult, E. F. Colecchia, M. L'Hermite-Baleriaux, Z. Nie, G. Copinschi, and E. Van Cauter Adaptation of the 24-h growth hormone profile to a state of sleep debt Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R874 - R883. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, T. Kamioka, M. Hosaka, K. Mabuchi, A. Mizuchi, Y. Shimazaki, M. Tsunoo, and T. Tanaka Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 601 - 606. [Abstract] [Full Text]

				J. A. Kanaley, M. M. Weatherup-Dentes, E. B. Jaynes, and M. L. Hartman Obesity Attenuates the Growth Hormone Response to Exercise J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3156 - 3161. [Abstract] [Full Text]

				N. Briard, M. Rico-Gomez, V. Guillaume, N. Sauze, V. Vuaroqueaux, F. Dadoun, Y. Le Bouc, C. Oliver, and A. Dutour Hypothalamic Mediated Action of Free Fatty Acid on Growth Hormone Secretion in Sheep Endocrinology, December 1, 1998; 139(12): 4811 - 4819. [Abstract] [Full Text] [PDF]

				C. Wagner, S. R. Caplan, and G. S. Tannenbaum Genesis of the ultradian rhythm of GH secretion: a new model unifying experimental observations in rats Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E1046 - E1054. [Abstract] [Full Text] [PDF]

				M. E. Wilson Regulation of the Growth Hormone-Insulin-Like Growth Factor I Axis in Developing and Adult Monkeys Is Affected by Estradiol Replacement and Supplementation with Insulin-Like Growth Factor I J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2018 - 2028. [Abstract] [Full Text]

				E. Gevers, S. M. Pincus, I. C. A. F. Robinson, and J. D. Veldhuis Differential orderliness of the GH release process in castrate male and female rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R437 - R444. [Abstract] [Full Text] [PDF]

				M. Tzanela, C. Wagner, and G. Shaffer Tannenbaum Recombinant Human Growth Hormone-Binding Protein Fails to Enhance the in Vivo Bioactivity of Human Growth Hormone in Normal Rats Endocrinology, December 1, 1997; 138(12): 5316 - 5324. [Abstract] [Full Text] [PDF]

				J. A. Kanaley, J. Y. Weltman, J. D. Veldhuis, A. D. Rogol, M. L. Hartman, and A. Weltman Human growth hormone response to repeated bouts of aerobic exercise J Appl Physiol, November 1, 1997; 83(5): 1756 - 1761. [Abstract] [Full Text] [PDF]

				E. Pellegrini, M. T. Bluet-Pajot, F. Mounier, P. Bennett, C. Kordon, and J. Epelbaum Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats J. Neurosci., December 15, 1996; 16(24): 8140 - 8148. [Abstract] [Full Text] [PDF]