This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lloyd, R. V. Articles by Frohman, L. A. Search for Related Content PubMed PubMed Citation Articles by Lloyd, R. V. Articles by Frohman, L. A.

American Journal of Pathology, Vol 141, 895-906, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis

RV Lloyd, L Jin, A Chang, E Kulig, SA Camper, BD Ross, TR Downs and LA Frohman
Department of Pathology, University of Michigan Medical Center, Ann Arbor.

Morphologic changes in the pituitary, liver, and pancreas of mice with the metallothionein-human growth hormone--releasing hormone (MT-hGRH) transgene were analyzed by in situ hybridization histochemistry (ISH). There was progression from somatotroph hyperplasia to neoplasia in pituitaries of transgenic mice. Pituitary neoplasms were present between 9 to 12 months of age in some mice. Magnetic resonance imaging (MRI) readily identified enlarged pituitaries in MT-hGRH transgenic mice. Serum mouse GH and hGRH levels were marked elevated in MT-hGRH transgenic mice. In situ hybridization histochemistry showed mRNA for hGRH in liver, pituitary, pancreas, spleen, and in most other tissues examined. Combined ISH and immunohistochemistry in the pituitary gland showed that some of the GH cells also produced hGRH, and ultrastructural immunohistochemical analysis of pituitaries showed that GH and hGRH were localized in the same cell and within the same secretory granules. Liver cells of MT-hGRH transgenic mice showed evidence of hypertrophy, and the pancreatic islets were hyperplastic with significant increases in the islet cell areas. The morphologic changes in the liver were distinctive enough to separate control littermates from MT-hGRH transgenic mice in all cases. The enlarged pancreatic islets had increased numbers of insulin-producing cells. Immunoreactive hGRH and hGRH mRNA were both localized in islet cells, and an intense hybridization signal of hGRH mRNA, but only weak staining for hGRH protein, were detected in the liver of transgenic mice. These results indicate that excessive hGRH production leads to distinct morphologic changes in various organs in MT-hGRH transgenic mice and that there is temporal progression from hyperplasia to adenomatous somatotrophs in pituitaries with chronic stimulation by hGRH that involves paracrine, endocrine, and autocrine mechanisms.

This article has been cited by other articles:

				M. L. Brinkmeier, J. H. Stahl, D. F. Gordon, B. D. Ross, V. D. Sarapura, J. M. Dowding, S. K. Kendall, R. V. Lloyd, E. C. Ridgway, and S. A. Camper Thyroid Hormone-Responsive Pituitary Hyperplasia Independent of Somatostatin Receptor 2 Mol. Endocrinol., December 1, 2001; 15(12): 2129 - 2136. [Abstract] [Full Text] [PDF]

				R. D. Kineman, L. T. Teixeira, G. V. Amargo, K. T. Coschigano, J. J. Kopchick, and L. A. Frohman The Effect of GHRH on Somatotrope Hyperplasia and Tumor Formation in the Presence and Absence of GH Signaling Endocrinology, September 1, 2001; 142(9): 3764 - 3773. [Abstract] [Full Text] [PDF]

				S. L. Asa, M. A. Kelly, D. K. Grandy, and M. J. Low Pituitary Lactotroph Adenomas Develop after Prolonged Lactotroph Hyperplasia in Dopamine D2 Receptor-Deficient Mice Endocrinology, November 1, 1999; 140(11): 5348 - 5355. [Abstract] [Full Text]

				S. L. Asa and S. Ezzat The Cytogenesis and Pathogenesis of Pituitary Adenomas Endocr. Rev., December 1, 1998; 19(6): 798 - 827. [Abstract] [Full Text]

				M. A. Schwartz Integrins, Oncogenes, and Anchorage Independence J. Cell Biol., November 3, 1997; 139(3): 575 - 578. [Full Text] [PDF]

				M. Kovacs, R. D. Kineman, A. V. Schally, M. Zarandi, K. Groot, and L. A. Frohman Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) on GH and Insulin-Like Growth Factor I Levels in Transgenic Mice Overexpressing the Human GHRH Gene, an Animal Model of Acromegaly Endocrinology, November 1, 1997; 138(11): 4536 - 4542. [Abstract] [Full Text] [PDF]

				N. Sanno, A. Teramoto, R. Y. Osamura, S. Genka, H. Katakami, L. Jin, R. V. Lloyd, and K. Kovacs A Growth Hormone-Releasing Hormone-Producing Pancreatic Islet Cell Tumor Metastasized to the Pituitary Is Associated with Pituitary Somatotroph Hyperplasia and Acromegaly J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2731 - 2737. [Abstract] [Full Text] [PDF]