1. FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes
- Author
-
Varykina G. Thackray and Danalea V. Skarra
- Subjects
medicine.medical_treatment ,FOXO1 ,Gonadotrophs ,Medical and Health Sciences ,Biochemistry ,Gonadotropin-Releasing Hormone ,Mice ,Endocrinology ,2.1 Biological and endogenous factors ,Insulin ,Aetiology ,Insulin-Like Growth Factor I ,Phosphorylation ,Forkhead Box Protein O1 ,IGF1 ,Diabetes ,food and beverages ,Forkhead Transcription Factors ,Biological Sciences ,Protein Transport ,Gonadotropin ,hormones, hormone substitutes, and hormone antagonists ,endocrine system ,medicine.medical_specialty ,medicine.drug_class ,1.1 Normal biological development and functioning ,Biology ,Gonadotropic cell ,digestive system ,Article ,Cell Line ,Gonadotrope ,Endocrinology & Metabolism ,Underpinning research ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Protein kinase B ,Protein Processing ,PI3K/AKT/mTOR pathway ,Forkhead box O1 ,Agricultural and Veterinary Sciences ,Akt/PKB signaling pathway ,Post-Translational ,nutritional and metabolic diseases ,GnRH ,Protein Processing, Post-Translational ,Proto-Oncogene Proteins c-akt - Abstract
The FOXO1 transcription factor is important for multiple aspects of reproductive function. We previously reported that FOXO1 functions as a repressor of gonadotropin hormone synthesis, but how FOXO1 is regulated in pituitary gonadotropes is unknown. The growth factors, insulin and insulin-like growth factor I (IGF1), function as key regulators of cell proliferation, metabolism and apoptosis in multiple cell types through the PI3K/AKT signaling pathway. In this study, we found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FOXO1 relocation from the nucleus to the cytoplasm. Furthermore, insulin administration in vivo induced phosphorylation of FOXO1 and AKT in the pituitary. Thus, insulin and IGF1 act as negative regulators of FOXO1 activity and may serve to fine-tune gonadotropin expression.
- Published
- 2015