Somatotropes maintain their immature cells through Insulin-like growth factor I (IGF-I)

• Published in: Endocrine pathology 2007-09, Vol.18 (3), p.174-181
• Main Authors: Yokoyama, Kotaro, Mogi, Chihiro, Miura, Kaoru, Kuroda, Keisuke, Inoue, Kinji
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Brain tumors; Cell Proliferation - drug effects; Cells; Culture Media, Conditioned - pharmacology; Disease Progression; Dose-Response Relationship, Drug; Growth hormone; Growth Hormone - genetics; Growth Hormone - metabolism; Growth hormones; Human Growth Hormone - pharmacology; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - physiology; Insulin-like growth factors; Microenvironments; Pituitary; Pituitary Neoplasms - pathology; Progenitor cells; Rats; RNA, Messenger - metabolism; Rodents; Signal Transduction - drug effects; Somatotrophs - metabolism; Somatotrophs - pathology; Stem cells; Stem Cells - metabolism; Stem Cells - pathology; Tumor Cells, Cultured
• ISSN: 1046-3976; 1559-0097
• DOI: 10.1007/s12022-007-0016-6

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.