Abstract
The effect of GRH infusion on rat adenohypophysial morphology was studied by light microscopy, immunocytochemistry, in situ hybridization, and electron microscopy. Synthetic rat GRH was intravenously administered by osmotic minipumps at 14.4, 72, 360 and 720 μg/ day/rat for 1 week. In one group treated for 1 week with a daily dose of 720 μg GRH, the rats were killed 7 days after withdrawal of GRH. Control rats in which GRH was replaced by excipient, or those that received no treatment, were included as well. GRH infusion with daily doses of 360 and 720 μg resulted in a significant increase in pituitary weight and weaker GH immunoreactivity compared with other groups. Ultrastructurally, the somatotrophs were increased in size and became sparsely granulated, and the organelles involved in hormone sythesis were very prominent. The intensity of the GH mRNA signal did not differ from control animals, suggesting the desensitization of somatotrophs to GRH. The highest GRH dose induced an increased number of nuclei immunoreactive for proliferation cell nuclear antigen (PCNA). One week after GRH withdrawal, shrinkage of cytoplasm, involution of RER and Golgi complex, and a decrease of cell attachment sites indicated the reversibility of changes induced by GRH. In conclusion, GRH infusion induced, within days, hypertrophy and proliferation of somatotrophs with ultrastructural features of highly stimulated, sparsely granulated cells. Morphological changes were reversible.Endocr Pathol 4:131–139, 1993.
Similar content being viewed by others
References
Asa SL, Kovacs K, Stcfancanu L, Horvath E, Billestrup N, Gonzalcz-Manchon C, Vale W. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone. Endocrinology 131:2083–2089, 1993.
Asa SL, Kovacs K, Stcfaneanu L, Horvath E, Billestrup N, Gonzalez-Manchon C, Vale W. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone. Proc Soc Exp Biol Med 193:232–235, 1990.
Barinaga M, Yamomoto G, Rivier C, Vale W, Evans R, Rosenfeld MG. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature 306:84–85, 1983.
Bendayan M. Double immunocytochemical labeling applying the protein A-gold technique. J Histochem Cytochem 30:81–85, 1982.
Bilezikjian LH, Vale W. Chronic exposure of cultured rat anterior pituitary cells to GRF causes partial loss of responsiveness to GRH. Endocrinology 115:2032–2034, 1984.
Billestrup N, Swanson LW, Vale W. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc Natl Acad Sci USA 83:6854–6857, 1986.
Ceda GP, Hoffman AR. Growth hormone-releasing factor desensitization in rat anterior pituitary cells in vitro. Endocrinology 116:1334–1340, 1985.
Couch EF, Arimura A, Schally AV, Saito M, Sawano S. Electron microscope studies of somatotrophs of rat pituitary after injection of purified growth hormone. Endocrinology 85:1084–1091, 1969.
Cronin MJ, Burnier J, Clark RG. Growth hormone releasing hormone infusion in normal rats enlarges the pituitary within days. J Endocrinol Invest 14(suppl 2):34, 1991.
De Virgilus G, Meldolesi J, Clementi F. Ultrastructure of growth hormone-producing cells of rat pituitary after injections of hypothalamic extract. Endocrinology 83: 1278–1284, 1988.
Drazin B, Dahl R, Sherman N, Sussman KE, Staehelin LA. Exocytosis in normal anterior pituitary cells. J Clin Invest 81:1042–1050, 1988.
Felix IA, Horvath E, Kovacs K, Smyth HS, Killinger DW, Dale J. Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphologic study including immunoelectron microscopy. Acta Neuropathol 71:76–82, 1986.
Frohman LA, Jansson J-O. Growth hormone-releasing hormone. Endocr Rev 9: 357–373, 1968.
Gick GG, Zeytin FN, Brazeau P, Ling NC, Esch FS, Bancroft C. Growrth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci USA 81:1553–1555, 1984.
Hsu SM, Raine L, Fanger H. The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821, 1981.
Mayo KE, Hammer RE, Swanson LW, Brinster RL, Rosenfeld MG, Evans RM. Dramatic pituitary hyperplasia in transgenic mice expressing a human growth hormone-releasing factor gene. Mol Endocrinol 2:606–612, 1988.
McComb DJ, Kovacs K, Beri J, Zak F. Pituitary adenomas in old Sprague-Dawley rats: a histologic, ultrastructural, and immunocytochemical study. J Natl Cancer Inst 73:1143–1166, 1984.
Ramsay JA, Kovacs K, Asa SL, Pike MJ, Thorner MO. Reversible sellar enlargement due to growth hormnone-releasing hormone production by pancreatic endoocrine tumors in an acromegalic patient with multiple endocrine neoplasia type I syndrome. Cancer 62:445–450, 1988.
Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tu- mors: clinical, biochemical, and morphological manifestations. Endocr Rev 9:357–373, 1988.
Schally AV, Mullcr EE, Sawano S. Effect of porcine growth hormone-releasing factor on the release and synthesis of growth hormone in vitro. Endocrinology 82:271–276, 1968.
Shimada O, Tosaka-Shimada H. Morphological analysis of growth hormone release from rat somatotrophs into blood vessels by immunogold electron microscopy. Endocrinology 125:2677–2682, 1989.
Stefaneanu L, Kovacs K, Horvath E, Asa SL, Losinski NE, Billestrup N, Price J, Vale W. Adenohypophysial changes in mice trans-genic for human growth hormone-releasing factor: a histologic, immunocytochemical, and electron microscopic investigation. Endocrinology 125:2710–2718, 1989.
Stefaneanu L, Rindi G, Horvath E, Murphy D, Polak JM, Kovacs K. Morphology of adenohypophysial tumors in mice trans-genic for vasopressin-SV40 hybrid onco-gene. Endocrinology 130:1787–1795, 1992.
Wehrenberg WB, Brazeau P, Ling N, Textor G, Guillemain R. Pituitary growth hormone response in rats during a 24 hour infusion of growth hormone-releasing factor. Endocrinology 114:1613–1616, 1984.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stefaneanu, L., Kovacs, K., Horvath, E. et al. Effect of intravenous infusion of growth hormone-releasing hormone on the morphology of rat pituitary somatotrophs. Endocr Pathol 4, 131–139 (1993). https://doi.org/10.1007/BF02915301
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02915301