PMON144 FOXO1 is required for glucocorticoid induced somatotrope maturation

The pituitary somatotrope is responsible for the secretion of growth hormone (GH). GH deficiency (GHD) affects 1 in 4000 to 1 in 10,000 live births and can manifest as a partial or complete insufficiency of GH from the pituitary gland. Evidence shows that GH secretion can be directed by several transcription factors (TF) and some hormones such as glucocorticoids that play the main role not only in somatotrope maturation but also maintenance of function. We found that FOXO1 is required in glucocorticoid induction of important somatotrope genes. Inducing somatotrope-derived MtT/S cells, with glucocorticoid for 96 hours, showed upregulation of Gh1, Ghrhr, Foxo1, and the calcium binding protein, C2cd4a. Deletion of Foxo1 from MtT/S cells using CRISPR/Cas-9 impairs basal and glucocorticoid-induced expression of Gh1 and C2cd4a, but does not impair expression of Ghrhr. GH protein is also reduced in Foxo1 deleted clones compared to control. In mice, we find that dexamethasone, a synthetic glucocorticoid, can stimulate premature somatotrope maturation at e15.75. Evidence of premature maturation includes presence of GH protein and increased expression of Gh1. To sum up, these data demonstrate that FOXO1 may be an important factor mediating glucocorticoid induction of somatotrope maturation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.