NR3C1 is required for normal somatotrope differentiation and Foxo1 expression in pituitary
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Pratyusa Das Ridwanullah A Abubakar Nooshin Mojahed Dania Abou-Jabal Prisha Kittu Michelle L Brinkmeier Jessica Olsen Dale Ann Sunny Sally A Camper Robin Lovell-Badge Karine Rizzoti Buffy S EllsworthAbstract
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 current 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 five days after birth. The number of somatotropes remains reduced at seven weeks of age in females and males, but lactotrope cell numbers are only increased 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.
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Journal
Endocrinology
Volume
167
Issue number
7
Pages
bqag060
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10.1210/endocr/bqag060
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42141901
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42141901
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