Endocrinology, Vol 137, 1013-1018, Copyright © 1996 by Endocrine Society

ARTICLES

Growth, growth hormone (GH)-binding protein, and GH receptors are differentially regulated by peak and trough components of the GH secretory pattern in the rat

EF Gevers, JM Wit and IC Robinson
National Institute for Medical Research, London, UK.

Body growth, GH secretory pattern, hepatic GH receptor (GHR), and plasma GH-binding protein (GHBP) levels are all sexually dimorphic in the rat. Male rats grow faster than females, and in GH-deficient animals, GH therapy is more effective when given in a pulsatile pattern rather than a continuous infusion. This contrasts with GHBP and hepatic GHR levels, which are lower in males than in females and raised by continuous but not pulsatile GH therapy. One possible explanation is that growth is primarily regulated by GH pulses, whereas GHR and GHBP are regulated mostly by the trough levels (which are lower in males than in females). To test this hypothesis directly, GH-deficient dwarf rats were given patterned iv infusions of hGH in which the relative contributions of the peak and trough components of the GH pattern were systematically varied, independently of dose, and their effects on weight and length gain, plasma GHBP, and hepatic GHR binding were measured. We found that the dose-response curves for GH given by pulsatile vs. continuous infusion were significantly nonparallel, and that growth was primarily stimulated by the pulsatile component of a mixed GH infusion pattern; doubling the GH dose by adding a continuous (c) infusion to a series of pulses (p) neither enhanced nor inhibited weight gain (36 micrograms hGH/day pulses (36p) vs. 36 micrograms hGH/day pulses + 36 micrograms hGH/day continuously (36p + 36c):0.9 +/- 0.2 g/day vs. 1.1 +/- 0.2 g/day), whereas doubling the GH dose by adding a pulsatile component significantly enhanced growth (72p:2.1 +/- 0.2 g/day, P < 0.01). Conversely, hepatic GHR and plasma GHBP levels were highly sensitive to the continuous element of the mixed infusion pattern and were totally unaffected by varying the pulsatile component over a wide range of doses. These results strongly suggest that growth and hepatic GHR/plasma GHBP respond differentially to the peak and trough components of the GH secretion pattern in the rat.

This article has been cited by other articles:

				L. S. Farhy and J. D. Veldhuis Putative GH pulse renewal: periventricular somatostatinergic control of an arcuate-nuclear somatostatin and GH-releasing hormone oscillator Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1030 - R1042. [Abstract] [Full Text] [PDF]

				R. P. Radcliff, M. J. VandeHaar, Y. Kobayashi, B. K. Sharma, H. A. Tucker, and M. C. Lucy Effect of Dietary Energy and Somatotropin on Components of the Somatotropic Axis in Holstein Heifers J Dairy Sci, May 1, 2004; 87(5): 1229 - 1235. [Abstract] [Full Text] [PDF]

				N. R. Biermasz, A. M. Pereira, M. Frolich, J. A. Romijn, J. D. Veldhuis, and F. Roelfsema Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E25 - E30. [Abstract] [Full Text]

				M. P. P. Geary, P. J. Pringle, C. H. Rodeck, J. C. P. Kingdom, and P. C. Hindmarsh Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3708 - 3714. [Abstract] [Full Text] [PDF]

				N. Balthasar, P.-F. Mery, C. B. Magoulas, K. E. Mathers, A. Martin, P. Mollard, and I. C. A. F. Robinson Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH-Enhanced Green Fluorescent Protein Transgenic Mice: A Ventral Hypothalamic Network Endocrinology, June 1, 2003; 144(6): 2728 - 2740. [Abstract] [Full Text] [PDF]

				E. F. Gevers, N. Loveridge, and I. C. A. F. Robinson Bone Marrow Adipocytes: A Neglected Target Tissue for Growth Hormone Endocrinology, October 1, 2002; 143(10): 4065 - 4073. [Abstract] [Full Text] [PDF]

				W. J. Wallen, M. P. Belanger, and C. Wittnich Sex Hormones and the Selective Estrogen Receptor Modulator Tamoxifen Modulate Weekly Body Weights and Food Intakes in Adolescent and Adult Rats J. Nutr., September 1, 2001; 131(9): 2351 - 2357. [Abstract] [Full Text] [PDF]

				W. M. Drake, S. J. Howell, J. P. Monson, and S. M. Shalet Optimizing GH Therapy in Adults and Children Endocr. Rev., August 1, 2001; 22(4): 425 - 450. [Abstract] [Full Text] [PDF]

				J.-L. Liu, S. Yakar, and D. LeRoith Mice Deficient in Liver Production of Insulin-Like Growth Factor I Display Sexual Dimorphism in Growth Hormone-Stimulated Postnatal Growth Endocrinology, December 1, 2000; 141(12): 4436 - 4441. [Abstract] [Full Text] [PDF]

				G. Van den Berghe, R. C. Baxter, F. Weekers, P. Wouters, C. Y. Bowers, and J. D. Veldhuis A Paradoxical Gender Dissociation within the Growth Hormone/Insulin-Like Growth Factor I Axis during Protracted Critical Illness J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 183 - 192. [Abstract] [Full Text]

				P. C. Hindmarsh, E. Dennison, S. M. Pincus, C. Cooper, C. H. D. Fall, D. R. Matthews, P. J. Pringle, and C. G. D. Brook A Sexually Dimorphic Pattern of Growth Hormone Secretion in the Elderly J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2679 - 2685. [Abstract] [Full Text]

				K. Jandziszak, C. Suarez, E. Wasserman, R. Clark, B. Baker, F. Liu, R. Hintz, P. Saenger, and L. P. Brion Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1998; 275(1): R120 - R128. [Abstract] [Full Text] [PDF]

				E. Pellegrini, D. F. Carmignac, M. T. Bluet-Pajot, F. Mounier, P. Bennett, J. Epelbaum, and I. C. A. F. Robinson Intrahypothalamic Growth Hormone Feedback: From Dwarfism to Acromegaly in the Rat Endocrinology, November 1, 1997; 138(11): 4543 - 4551. [Abstract] [Full Text] [PDF]

				R. G. Smith, L. H. T. Van der Ploeg, A. D. Howard, S. D. Feighner, K. Cheng, G. J. Hickey, M. J. Wyvratt Jr., M. H. Fisher, R. P. Nargund, and A. A. Patchett Peptidomimetic Regulation of Growth Hormone Secretion Endocr. Rev., October 1, 1997; 18(5): 621 - 645. [Abstract] [Full Text]

				P. C. Hindmarsh, C. H. D. Fall, P. J. Pringle, C. Osmond, and C. G. D. Brook Peak and Trough Growth Hormone Concentrations Have Different Associations with the Insulin-Like Growth Factor Axis, Body Composition, and Metabolic Parameters J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2172 - 2176. [Abstract] [Full Text] [PDF]

				C. A. Gebert, S.-H. Park, and D. J. Waxman Regulation of Signal Transducer and Activator of Transcription (STAT) 5b Activation by the Temporal Pattern of Growth Hormone Stimulation Mol. Endocrinol., April 1, 1997; 11(4): 400 - 414. [Abstract] [Full Text]