Somatotropes Maintain Their Immature Cells Through Insulin-like Growth Factor I (IGF-I)

A pituitary tumor is considered to be composed of a heterogeneous population of hormone-producing endocrine cells, folliculo-stellate (FS) cells, and potential hormone-inactive progenitor cells to maintain a microenvironment such as that in angiogenesis for tumor development cooperatively. However, the system that maintains such a heterogeneous cell population has not been clarified yet. In the present study, we examined the mechanism for maintaining a heterogeneous cell population using two rat cell lines, MtT/S and MtT/E cells, which are known growth hormone (GH)-producing cells, and their progenitor cells, respectively. We found that conditioned medium of MtT/S cells could stimulate the growth of MtT/E cells. In addition, GH and insulin-like growth factor I (IGF-I) stimulated the growth of MtT/E cells. The messenger RNAs (mRNAs) of receptors for IGF-I and GH were expressed in the MtT/E cells. Moreover, IGF-I receptor inhibitor AG1024 could abolish the growth stimulatory activity in the conditioned medium of MtT/S cells. Therefore, we concluded that somatotropes (MtT/S) maintain their progenitor cells (MtT/E) through the GH–IGF-I signaling and IGF-I directly, which might be involved in the maintenance of progenitors of GH-producing cells and might contribute to pituitary tumor development.