NR3C1 is required for normal somatotrope differentiation and <i>Foxo1</i> expression in pituitary

Glucocorticoids are an important signal for the differentiation of many types of cells. Consistent with this, several studies have demonstrated that glucocorticoids promote the somatotrope differentiation program and functionality. Interestingly, we previously found that loss of the forkhead factor, FOXO1, results in delayed emergence of somatotropes and prevents glucocorticoid-induced premature differentiation of somatotropes. In the present study, we find that pituitary-specific deletion of Nr3c1, the gene encoding the glucocorticoid receptor, impairs somatotrope differentiation and increases lactotrope numbers embryonically and at 5 days after birth. The number of somatotropes remains reduced at age 7 weeks in females and males, but lactotrope cell numbers are increased only in females at this age. FOXO1 is nearly undetectable in pituitary glands from mouse embryos lacking NR3C1 and continues to be reduced in adults. These findings suggest that glucocorticoids are an important signal for determining the balance between somatotropes and lactotropes and that FOXO1 may mediate NR3C1 induction of somatotrope differentiation.