Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene

Pituitary is influenced by circulating and locally produced insulinlike gro wth factor I (IGF-I). To further elucidate the role of pituitary IGF-I, we compared pituitary morphology of homozygous (IgfI(-/-)), heterozygous (IgfI (+/-)), and wild-type (IgfI(+/+)) fetal and adult mice using light microsco py, immunocytochemistry, in situ hybridization and electron microscopy. In pituitaries of Igf1(-/-) and Igf1(+/-) fetal mice (day 18.5) GH RNA signal was decreased. In Igf1(-/-) adult females, GH cells were significantly dimi nished in size; GH RNA signal was stronger in Igf1(-/-) mice compared with IgfI(+/+) mice, and the somatotrophs had ultrastructural features of stimul ation. The number of PRL cells and PRL hybridization signal were significan tly decreased, however plasma PRL levels were elevated in both genders. No changes in other cell types in Igf1(-/-) mice, and no alterations in Igf1(/-) mice were evident. IGF-I treatment for 2 weeks of Igf1(-/-) mice increa sed significantly body weights, decreased GH hybridization signal, and had no effect on PRL cells, or PRL plasma levels, whereas in IgfI(+/+) mice, PR L RNA signal and PRL plasma levels were markedly increased. In conclusion, IGF-I plays no role in differentiation of pituitary cells, affects the size of somatotrophs in females, and is a stimulator of lactotrophs in both gen ders.