TY - JOUR

T1 - Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor

T2 - a histological, immunocytochemical, and electron microscopic investigation

AU - Stefaneanu, L

AU - Kovacs, K

AU - Horvath, E

AU - Asa, S L

AU - Losinski, N E

AU - Billestrup, Nils

AU - Price, J

AU - Vale, W

PY - 1989/11

Y1 - 1989/11

N2 - The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed, and the markedly enlarged pituitaries were studied by histology, immunocytochemistry, electron microscopy, and immunogold method, using double labeling at ultrastructural level. In all pituitaries, a massive hyperplasia, chiefly of mammosomatotrophs, was found. These bihormonal cells, containing GH and PRL, were demonstrated by light microscopy and ultrastructural immunocytochemistry. Electron microscopy revealed the presence of cells with characteristics of GH cells in three pituitaries and cells resembling human adenomatous mammosomatotrophs in the other three glands. All of these cells, regardless of their ultrastructural features, contained secretory granules heavily labeled for GH by immunogold technique; PRL labeling varied from cell to cell, with the predominance of a weak immunostaining and was colocalized with GH in secretory granules. These results indicate that chronic exposure to GRF excess leads to mammosomatotroph hyperplasia. It is suggested that GH cells proliferate and transform to mammosomatotrophs in response to GRF stimulation. Focal PRL cell hyperplasia noted in three pituitaries could also be due to a GRF effect. Longer exposure to GRF is needed to clarify whether GRF can cause adenoma.

AB - The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed, and the markedly enlarged pituitaries were studied by histology, immunocytochemistry, electron microscopy, and immunogold method, using double labeling at ultrastructural level. In all pituitaries, a massive hyperplasia, chiefly of mammosomatotrophs, was found. These bihormonal cells, containing GH and PRL, were demonstrated by light microscopy and ultrastructural immunocytochemistry. Electron microscopy revealed the presence of cells with characteristics of GH cells in three pituitaries and cells resembling human adenomatous mammosomatotrophs in the other three glands. All of these cells, regardless of their ultrastructural features, contained secretory granules heavily labeled for GH by immunogold technique; PRL labeling varied from cell to cell, with the predominance of a weak immunostaining and was colocalized with GH in secretory granules. These results indicate that chronic exposure to GRF excess leads to mammosomatotroph hyperplasia. It is suggested that GH cells proliferate and transform to mammosomatotrophs in response to GRF stimulation. Focal PRL cell hyperplasia noted in three pituitaries could also be due to a GRF effect. Longer exposure to GRF is needed to clarify whether GRF can cause adenoma.

KW - Animals

KW - Cloning, Molecular

KW - Female

KW - Growth Hormone

KW - Growth Hormone-Releasing Hormone

KW - Humans

KW - Hyperplasia

KW - Hypertrophy

KW - Immunohistochemistry

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Microscopy, Electron

KW - Pituitary Gland, Anterior

KW - Prolactin

U2 - 10.1210/endo-125-5-2710

DO - 10.1210/endo-125-5-2710

M3 - Journal article

C2 - 2507296

VL - 125

SP - 2710

EP - 2718

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 5

ER -