An Immunocytochemical and Ultrastructural Study of Adenohypophyses of Mice Transgenic for Human Growth Hormone*

Abstract

Adenohypophysial morphology in 12 mice transgenic for methallothionein-I-human (h) GH fusion gene was investigated by immunocytochemistry and electron microscopy. The sustained oversecretion of hGH stimulated body growth. The pituitary glands of 6-month-old transgenic mice were significantly decreased in weight and showed marked morphological changes in somatotrophs, lactotrophs, corticotrophs, and gonadotrophs. GH-immunoreactive cells were greatly reduced in size and midly decreased in number; by electron microscopy, the organelles implicated in hormone synthesis were inconspicuous in this cell type. Transgenic males were hypoprolactinemic, presumably due to lactogenic activity of hGH in rodents. Their pituitaries displayed few and slender PRL-immunoreactive cells; ultrastructurally, they belonged to immature (type II) lactotrophs. However, in females, PRL-containing cells showed no change in number, size, or distribution compared to controls. Prior biochemical studies demonstrated high blood levels of LH in males. Their pituitaries contained highly active gonadotrophs resembling gonadectomy cells, consistent with the view that these changes are related to PRL-like activity of hGH in mice. In both sexes, stimulated corticotrophs were present. The results indicate that some changes in adenohypophysial cells of mice transgenic for hGH can be attributed to protracted overproduction of the heterologous GH, whereas others can be explained by lactotrophic activity of hGH in mice. The divergent morphological responses of lactotrophs and gonadotrophs in the two sexes may reflect differences in the hormonal regulatory mechanisms between male and female mice.