title: Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the secretory and proliferative activity of rat adrenocortical cells in the presence of proteasome inhibitors.
abstract: Sporadic findings indicate that proteolysis may affect steroid secretion in rat ovary granulosa cells. We examined the effects of the proteasome inhibitors MG115 and MG101 on the in vitro secretion and growth of rat adrenocortical cells. MG115 and/or MG101 decreased within 120 min the aldosterone and corticosterone secretion from freshly dispersed zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells. After a 24-h incubation MG115 alone or with MG101 lowered corticosterone production and enhanced proliferation rate of cultured ZF/R cells, while MG101 was per se ineffective. Real-time polymerase chain reaction demonstrated that MG101 decreased steroidogenic acute regulatory protein (StAR) mRNA in cultured cells. MG115 was per se ineffective, but when added together with MG101 evoked a marked rise in StAR mRNA content. In light of the present findings, we conclude that i) protein breakdown by proteasomes is required for the maintenance of a normal secretory and proliferative activity of freshly dispersed or cultured rat adrenocortical cells; and ii) in long-term experiments, great caution must be taken in correlating StAR mRNA content and steroidogenic capacity.
authors.affiliation: Department of Histology and Embryology, Karol Marcinkowski University of Medical Sciences, PL-60781 Poznan, Poland.
authors.forename: Agnieska
authors.initials: A
authors.lastname: Ziolkowska
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tortorella
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
authors.forename: Marcin
authors.initials: M
authors.lastname: Rucinski
authors.forename: Mariola
authors.initials: M
authors.lastname: Majchrzak
authors.forename: Ludwik K
authors.initials: LK
authors.lastname: Malendowicz
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics*; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D007976:Leupeptins; C502028:N-acetylleucyl-leucyl-norleucine; D009842:Oligopeptides; D010750:Phosphoproteins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; C089486:carbobenzoxy-leucyl-leucyl-norvalinal; D000098682:Steroidogenic Acute Regulatory Protein; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D004121:Dimethyl Sulfoxide