Global profiles of gene expression induced by adrenocorticotropin in Y1 mouse adrenal cells.
ACTH regulates the steroidogenic capacity, size, and structural integrity of the adrenal cortex through a series of actions involving changes in gene expression; however, only a limited number of ACTH-regulated genes have been identified, and these only partly account for the global effects of ACTH on the adrenal cortex. In this study, a National Institute on Aging 15K mouse cDNA microarray was used to identify genome-wide changes in gene expression after treatment of Y1 mouse adrenocortical cells with ACTH. ACTH affected the levels of 1275 annotated transcripts, of which 46% were up-regulated. The up-regulated transcripts were enriched for functions associated with steroid biosynthesis and metabolism; the down- regulated transcripts were enriched for functions associated with cell proliferation, nuclear transport and RNA processing, including alternative splicing. A total of 133 different transcripts, i.e. only 10% of the ACTH-affected transcripts, were represented in the categories above; most of these had not been described as ACTH-regulated previously. The contributions of protein kinase A and protein kinase C to these genome-wide effects of ACTH were evaluated in microarray experiments after treatment of Y1 cells and derivative protein kinase A-defective mutants with pharmacological probes of each pathway. Protein kinase A-dependent signaling accounted for 56% of the ACTH effect; protein kinase C-dependent signaling accounted for an additional 6%. These results indicate that ACTH affects the expression profile of Y1 adrenal cells principally through cAMP- and protein kinase A- dependent signaling. The large number of transcripts affected by ACTH anticipates a broader range of actions than previously appreciated.
Schimmer
Bernard P
BP
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada. bernard.schimmer@utoronto.ca
Cordova
Martha
M
Cheng
Henry
H
Tsao
Andrew
A
Goryachev
Andrew B
AB
Schimmer
Aaron D
AD
Morris
Quaid
Q
D000302:Adrenal Cortex / Q000166:cytology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D005786:Gene Expression Regulation; D016678:Genome; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C