role of amp-activated protein kinase on steroid hormone biosynthesis in adrenal nci-h295r cells活化蛋白激酶的作用在肾上腺类固醇激素生物合成nci-h295r细胞.pdfVIP

Role of AMP-Activated Protein Kinase on Steroid Hormone Biosynthesis in Adrenal NCI-H295R Cells 1,2 1,3 ´ 1,2 1,2 1,2 Andrea Hirsch , Dagmar Hahn , Petra Kempna , Gaby Hofer , Primus E. Mullis , Jean-Marc 1,2,3 ¨ 1,2 Nuoffer , Christa E. Fluck * 1 Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, University Hospital, University of Bern, Bern, Switzerland, 2 Department of Clinical Research, Inselspital, University Hospital, University of Bern, Bern, Switzerland, 3 Institute of Clinical Chemistry, Inselspital, University Hospital, University of Bern, Bern, Switzerland Abstract Regulation of human androgen biosynthesis is poorly understood. However, detailed knowledge is needed to eventually solve disorders with androgen dysbalance. We showed that starvation growth conditions shift steroidogenesis of human adrenal NCI-H295R cells towards androgen production attributable to decreased HSD3B2 expression and activity and increased CYP17A1 phosphorylation and 17,20-lyase activity. Generally, starvation induces stress and energy deprivation that need to be counteracted to maintain proper cell functions. AMP-activated protein kinase (AMPK) is a master energy sensor that regulates cellular energy balance. AMPK regulates steroidogenesis in the gonad. Therefore, we investigated whether AMPK is also a regulator of adrenal steroidogenesis. We hypothesized that starvation uses AMPK signaling to enhance androgen production in NCI-H295R cells. We found that AMPK subunits are expressed in NCI-H295 cells, normal adrenal tissue and human as well as pig ov