Endocrinology, Vol 124, 1380-1388, Copyright © 1989 by Endocrine Society

ARTICLES

Paradoxical enhancement of pituitary growth hormone (GH) responsiveness to GH-releasing factor in the face of high somatostatin tone

GS Tannenbaum, JC Painson, AM Lengyel and P Brazeau
Neuropeptide Physiology Laboratory, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.

Pituitary GH secretion is regulated by a delicate interplay between stimulatory (GRF) and inhibitory [somatostatin (SRIF)] hypothalamic hormones, although the nature of the GRF/SRIF interaction remains to be elucidated. In the present study, we documented a significant elevation of plasma SRIF-like immunoreactivity in 72-h fasted rats compared to that in fed controls (129.0 +/- 17.9 vs. 38.2 +/- 5.8 pg/ml; P less than 0.01) and used this model of high SRIF tone to further delineate the interrelation between GRF and SRIF in physiological regulation of pulsatile GH secretion. We examined pituitary GH responsiveness to GRF, both in vivo and in vitro, after 72-h exposure to nutritional deprivation and high SRIF secretion. In vivo, GRF-induced GH release was markedly enhanced in the face of high circulating SRIF; freely moving, starved rats released 4- to 8-fold more GH than fed controls in response to rat GRF iv. In vitro, both basal and human GRF-induced GH release were augmented 2- to 4-fold in perifused dispersed anterior pituitary cells of starved rats compared to those in fed controls, and this enhanced responsiveness persisted in the presence of 10(-9) M SRIF. These results demonstrate that SRIF not only inhibits GH secretion stimulated by GRF, but that under different temporal conditions SRIF may act in a paradoxically positive manner to sensitize pituitary GH responsiveness to GRF. Such a cooperative interaction of the two peptides may be necessary to optimize pulsatile GH release. Our findings provide support for the hypothesis that the temporal patterning of hypothalamic GRF/SRIF signals to pituitary somatotrophs may be the major determinant for pulsatile GH secretion and, ultimately, body growth.

This article has been cited by other articles:

				R. M. Luque, S. Park, and R. D. Kineman Severity of the Catabolic Condition Differentially Modulates Hypothalamic Expression of Growth Hormone-Releasing Hormone in the Fasted Mouse: Potential Role of Neuropeptide Y and Corticotropin-Releasing Hormone Endocrinology, January 1, 2007; 148(1): 300 - 309. [Abstract] [Full Text] [PDF]

				E Kim, S Sohn, M Lee, J Jung, R D Kineman, and S Park Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes J. Endocrinol., February 1, 2006; 188(2): 263 - 270. [Abstract] [Full Text] [PDF]

				M. C. French, R. P. Littlejohn, G. J. Greer, W. E. Bain, J. C. McEwan, and D. J. Tisdall Growth hormone and ghrelin receptor genes are differentially expressed between genetically lean and fat selection lines of sheep J Anim Sci, February 1, 2006; 84(2): 324 - 331. [Abstract] [Full Text] [PDF]

				C. D. McMahon, L. T. Chapin, K. J. Lookingland, R. P. Radcliff, and H. A. Tucker Feeding Reduces Activity of Growth Hormone-Releasing Hormone and Somatostatin Neurons Experimental Biology and Medicine, February 1, 2000; 223(2): 210 - 217. [Abstract] [Full Text]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]

				W. R. Baumbach, T. A. Carrick, M. H. Pausch, B. Bingham, D. Carmignac, I. C. A. F. Robinson, R. Houghten, C. M. Eppler, L. A. Price, and J. R. Zysk A Linear Hexapeptide Somatostatin Antagonist Blocks Somatostatin Activity In Vitro and Influences Growth Hormone Release in Rats Mol. Pharmacol., November 1, 1998; 54(5): 864 - 873. [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]