title: AMP-activated protein kinase regulates normal rat somatotroph cell function and growth of rat pituitary adenomatous cells.
abstract: AMP-activated protein kinase (AMPK) is activated under conditions that deplete cellular ATP and elevate AMP levels such as glucose deprivation and hypoxia. The AMPK system is primarily thought of as a regulator of metabolism and cell proliferation. Little is known about the regulation and the effects of AMPK in somatotroph cells. We present results from "in vitro" studies showing that AMPK activity has a role in regulating somatotroph function in normal rat pituitary and is a promising target for the development of new pharmacological treatments affecting cell proliferation and viability of pituitary adenomatous cells. In parallel, we show "in vivo" data obtained in the rat suggesting that AMPK is an intracellular transducer that may play a role in mediating the effects of the pharmacological treatment with dexamethasone on somatotrophs. In rat pituitary cell cultures, the AMP analog AICAR induced a rapid and clear-cut activation of AMPK. AICAR decreased GH release and total cellular GH content. An appropriate level of AMPK activation was essential for GH3 adenomatous cells. Remarkably, over-activation by AICAR induced apoptosis of GH3 whereas the AMPK inhibitor compound C was more effective at reducing cell proliferation. The role of endocrine or paracrine factors in regulating AMPK phosphorylation and activity in GH3 cells has been also studied. As to "in vivo" studies, western blot analysis revealed a significant decrease of phosphorylated AMPK alpha-subunit in pituitary homogenates of DEX-treated rats versus controls, suggesting reduced AMPK activity. In conclusion, our studies showed that AMPK has a role in regulating somatotroph function in normal rat pituitary and proliferation of pituitary adenomatous cells.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Unit of Pharmacology, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. tulipano@med.unibs.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tulipano
authors.forename: Michela
authors.initials: M
authors.lastname: Giovannini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Spinello
authors.forename: Valeria
authors.initials: V
authors.lastname: Sibilia
authors.forename: Andrea
authors.initials: A
authors.lastname: Giustina
authors.forename: Daniela
authors.initials: D
authors.lastname: Cocchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000494:pharmacology; D052683:Somatotrophs / Q000166:cytology*
chemical_list: D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D013006:Growth Hormone; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide