Adenohypophysial morphology in transgenic dwarf mice with cerebral production of human growth hormone. An immunocytochemical, in situ hybridization and ultrastructural study.

In transgenic mice with cerebral expression of foreign GH, pituitary GH production is profoundly disturbed, blood IGF-I levels are decreased and growth is retarded. Adenohypophysial morphology in these transgenic mice (6 males and 6 females) was studied by immunocytochemistry, in situ hybridization and electron microscopy. In both sexes, GH immunoreactive cells were smaller, and reduced in number by about 50% compared to controls; the decrease of GH mRNA signal was stronger in males than in females and by electron microscopy, the somatotrophs had the features consistent with suppressed endocrine activity. In both sexes, PRL immunoreactive cells were slightly decreased in number; in male pituitaries PRL mRNA signal was weak and ultrastructurally, only lactotrophs with small secretory granules were found. In the adenohypophyses of females, the intensity of hybridization signal for PRL mRNA was unchanged and ultrastructurally, the lactotrophs were slightly decreased in size and contained increased number of phagolysosomes. The number of ACTH immunoreactive cells was increased in males; however, the intensity of POMC mRNA was unchanged. The increase in number of LH immunoreactive cells appeared to be more pronounced in males. These changes resemble but are less prominent than those seen in mice transgenic for MT/hGH in which hGH is produced in many tissues, blood hGH and IGF-I are elevated and gigantism develops. Pituitary alterations are attributed to the indirect effects of hGH which is both somatotropic and lactogenic in mice.