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

• Published in: Molecular and cellular endocrinology 2014-03, Vol.383 (1-2), p.118-125
• Main Authors: Chen, Maopei, Wang, Zhiquan, Zhan, Ming, Liu, Ruixin, Nie, Aifang, Wang, Jiqiu, Ning, Guang, Ma, Qinyun
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - metabolism; Adiponectin - pharmacology; Adrenocorticotropic hormone (ACTH); Adrenocorticotropic Hormone - genetics; Adrenocorticotropic Hormone - metabolism; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - pharmacology; AMP-activated protein kinase (AMPK); AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Calcium - metabolism; Cell Line, Tumor; Corticotroph cells; Corticotrophs - cytology; Corticotrophs - metabolism; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Gene Expression Regulation; Humans; Hypothalamic–pituitary–adrenal axis (HPAA); Hypothalamo-Hypophyseal System - cytology; Hypothalamo-Hypophyseal System - metabolism; Male; Mice; Phosphorylation - drug effects; Pituitary-Adrenal System - cytology; Pituitary-Adrenal System - metabolism; Primary Cell Culture; Pyrazoles - pharmacology; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin - genetics; Receptors, Adiponectin - metabolism; Receptors, Corticotropin-Releasing Hormone; Ribonucleotides - pharmacology
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2013.12.007

•Adiponectin receptors are expressed in corticotroph cells.•Adiponectin stimulates basal ACTH release.•Adiponectin activates AMPK signalling in AtT-20 cells.•Adiponectin’s function in pituitary and HPAA was broadened. 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.