Immunohistochemical characterization of "hyperplasia-adenoma sequence" in the pituitaries of transgenic mice expressing a human growth hormone-releasing factor gene.

The morphology of hyperplastic pituitaries in seven human growth hormone-releasing factor (hGRF) transgenic mice were compared to those of two normal control mice. Under continuous stimulation by hGRF, both the total volume of the pituitary and the size of individual cells increased, and a nodular lesion, designated a "hypertrophic nodule", was identified. Immunohistochemically, the hyperplastic pituitaries consisted of various numbers of cells immunoreactive for rGH, rPRL, hACTH, rLH beta, hFSH beta, and r alpha SU, whereas the "hypertrophic nodule" was composed of rGH, rPRL, and rTSH beta positive cells, similar to the adenoma. The presence of the "hypertrophic nodule", which was intermediate in appearance between the controls and the adenomas, suggests a close relation between continuous hGRF stimulation and the development of a hyperplasia-adenoma sequence in the pituitary.