Interplay of NR3C1 and FOXO1 in somatotrope differentiation

Author

Pratyusa Das, Southern Illinois University CarbondaleFollow

Date of Award

12-1-2024

Degree Name

Doctor of Philosophy

Department

Molecular, Cellular, and Systemic Physiology

First Advisor

Ellsworth, Buffy

Abstract

This study investigates the molecular mechanisms governing pituitary gland development,focusing on the roles of transcription factors NR3C1 and FOXO1 in the differentiation and maturation of somatotropes, responsible for GH production. NR3C1, activated by glucocorticoids, is critical for somatotrope maturation and GH production, while FOXO1 plays a key role in mediating NR3C1’s effects. Disruptions in NR3C1 signaling impair somatotrope development, indicating its importance in maintaining normal pituitary function. Furthermore, FOXO1 is also essential for glucocorticoid-induced somatotrope maturation and GH expression, as demonstrated by in vitro and in vivo models where FOXO1 deficiency results in significantly reduced GH production. Additionally, FOXO1 regulates the heat shock protein Hsp90b1, a chaperone that stabilizes NR3C1, ensuring effective glucocorticoid signaling and proper somatotrope differentiation. This research provides a comprehensive understanding of how NR3C1 and FOXO1 interact to regulate pituitary development, highlighting a broader role of glucocorticoid signaling and its importance in maintaining molecular interactions necessary for somatotrope function.