Endocrinology, Vol 122, 2927-2932, Copyright © 1988 by Endocrine Society

ARTICLES

Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin

RW Holl, MO Thorner and DA Leong
Department of Internal Medicine, University of Virginia Medical Center, Charlottesville 22908.

The cytosolic free calcium concentration and cumulative GH release were measured simultaneously in normal pituitary cells. This was made possible by a novel combination of fluorescence microscopy using the calcium indicator fura-2 and a reverse hemolytic plaque assay. GRF (10 nM) rapidly increased the intracellular free calcium concentration ([ Ca2+]i) from a basal level of 234 +/- 17 nM (mean +/- SE) to a peak value of 480 +/- 61 nM 1 min after stimulation. This GRF-induced calcium rise was totally abolished in calcium-free medium or in the presence of calcium channel blockers cobalt chloride (2 mM) and verapamil (100 microM). When somatostatin (SRIF; 1 nM) was added after basal recordings, cytosolic calcium decreased to 96 +/- 23 nM in identified somatotropes. [Ca2+]i returned to baseline upon the removal of SRIF inhibition. This rebound was higher when a sequential treatment of SRIF followed by GRF was applied. Exposing cells to a combination of GRF (10 nM) plus SRIF (1 nM) resulted in a decrease in [Ca2+]i identical to that caused by SRIF treatment alone. Despite the 10-fold excess of GRF, SRIF not only inhibited hormone secretion, but also totally overcame the GRF-induced rise of [Ca2+]i. In summary, stimulation by GRF increases cytosolic calcium in normal somatotropes. This increase is proposed to be due to the influx of calcium through membrane ion channels. In contrast, SRIF decreases [Ca2+]i. This might explain the cAMP-independent effects of this peptide. The effect of SRIF dominates over that of GRF with respect to both changes in [Ca2+]i and hormone release. Changes in the GH secretory rate are, therefore, accompanied by parallel changes in [Ca2+]i, both of which are primarily regulated by SRIF.

This article has been cited by other articles:

				K. Tsaneva-Atanasova, A. Sherman, F. van Goor, and S. S. Stojilkovic Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory J Neurophysiol, July 1, 2007; 98(1): 131 - 144. [Abstract] [Full Text] [PDF]

				K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [Abstract] [Full Text] [PDF]

				J. L. Ramirez, F. Gracia-Navarro, S. Garcia-Navarro, R. Torronteras, M. M. Malagon, and J. P. Castano Somatostatin Stimulates GH Secretion in Two Porcine Somatotrope Subpopulations through a cAMP-Dependent Pathway Endocrinology, March 1, 2002; 143(3): 889 - 897. [Abstract] [Full Text] [PDF]

				C. J. H. Wong, J. D. Johnson, W. K. Yunker, and J. P. Chang Caffeine stores and dopamine differentially require Ca2+ channels in goldfish somatotropes Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2001; 280(2): R494 - R503. [Abstract] [Full Text] [PDF]

				T. Negishi, C. L. Chik, and A. K. Ho Ceramide Enhances Growth Hormone (GH)-Releasing Hormone-Stimulated Cyclic Adenosine 3',5'-Monophosphate Accumulation but Inhibits GH Release in Rat Anterior Pituitary Cells Endocrinology, December 1, 1999; 140(12): 5691 - 5697. [Abstract] [Full Text]

				T. L. Miller, P. A. Godfrey, V. I. DeAlmeida, and K. E. Mayo The Rat Growth Hormone-Releasing Hormone Receptor Gene: Structure, Regulation, and Generation of Receptor Isoforms with Different Signaling Properties Endocrinology, September 1, 1999; 140(9): 4152 - 4165. [Abstract] [Full Text]

				E. E. Muller, V. Locatelli, and D. Cocchi Neuroendocrine Control of Growth Hormone Secretion Physiol Rev, April 1, 1999; 79(2): 511 - 607. [Abstract] [Full Text] [PDF]

				N. Takasuka, M. R. H. White, C. D. Wood, W. R. Robertson, and J. R. E. Davis Dynamic Changes in Prolactin Promoter Activation in Individual Living Lactotrophic Cells Endocrinology, March 1, 1998; 139(3): 1361 - 1368. [Abstract] [Full Text] [PDF]

				C. Villalobos, W. J. Faught, and L. S. Frawley Dynamic Changes in Spontaneous Intracellular Free Calcium Oscillations and Their Relationship to Prolactin Gene Expression in Single, Primary Mammotropes Mol. Endocrinol., January 1, 1998; 12(1): 87 - 95. [Abstract] [Full Text]