Adiponectin regulates ACTH secretion and the HPAA in an AMPK-dependent manner in pituitary corticotroph cells

It is known that adipokines can regulate the hypothalamic-pituitary-adrenal axis (HPAA). In this study, we confirmed that adiponectin regulates the HPAA by affecting pituitary corticotroph cells. Using RT-PCR and immunofluorescence, we determined that adiponectin receptors were expressed in pituitary corticotroph tumour cells (AtT-20 cells and human corticotroph tumours). Adiponectin stimulated calcium influx and increased basal ACTH secretion without affecting corticotrophin-releasing hormone (CRH)-stimulated ACTH secretion, which was most likely due to the expression of adiponectin repressing CRH receptor 1 (CRHR1). Adiponectin also acutely stimulated ACTH release in primary culture pituitary cells. Lastly, adiponectin directly phosphorylated 5' AMP-activated protein kinase (AMPK) in AtT-20 cells. The effects of adiponectin were mimicked by AICAR, which was blocked by compound C. Taken together, our results suggested that adiponectin stimulated ACTH secretion and down-regulated CRHR1, possibly via an AMPK-dependent mechanism in pituitary corticotroph cells.