Molecular and Cellular Endocrinology 265–266 (2007) 102–107 Review A genome-wide assessment of adrenocorticotropin action in the Y1 mouse adrenal tumor cell line Bernard P. Schimmer a,b,∗ , Martha Cordova a , Henry Cheng a , Andrew Tsao a , Quaid Morris a,c a Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada M5G 1L6 b Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5G 1L6 c Department of Computer Sciences, University of Toronto, Toronto, Ontario, Canada M5G 1L6 Abstract This report summarizes the genome-wide effects of ACTH on transcript accumulation in mouse adrenal Y1 cells and the relative contributions of the cAMP-, protein kinase C- and Ca 2+ -dependent signaling pathways to these actions of the hormone. ACTH affected the accumulation of 1386 transcripts, a much larger number than previously appreciated. The cAMP signaling pathway accounted for approximately 56% of the ACTH effects whereas the protein kinase C- and Ca 2+ -dependent pathways made smaller contributions to ACTH action. Approximately 38% of the ACTH- affected transcripts could not be assigned to these signaling pathways and thus represent candidates for regulation via other mechanisms. The set of ACTH-regulated transcripts included clusters with functions in steroid metabolism, cell proliferation and alternative splicing. Collectively, our results suggest that Y1 adrenal cells undergo extensive remodeling upon prolonged stimulation with ACTH. The functional implications of ACTH on alternative splicing are explored. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: ACTH; Alternative splicing; cAMP; cDNA microarray; Protein kinase A; Protein kinase C; Y1 mouse adrenocortical tumor cells Contents 1. Introduction ............................................................................................................ 102 2. Effects of ACTH on transcript accumulation ............................................................................... 103 3. Mediators of the global actions of ACTH .................................................................................. 103 4. Functional implications of the global actions of ACTH ...................................................................... 104 5. Perspectives ............................................................................................................ 105 Acknowledgements ..................................................................................................... 106 Appendix A. Supplementary data ....................................................................................... 106 References ............................................................................................................. 106 1. Introduction The continuous action of ACTH on the adrenal cortex is essential for the maintenance of the size, cellular architecture and steroidogenic capacity of the fasciculata and reticularis zones of the gland and is commonly referred to as the trophic effect of the ∗ Corresponding author at: Banting and Best Department of Medical Research, University of Toronto, 112 College St., Toronto, Ontario, Canada M5G 1L6. Tel.: +1 416 978 6088; fax: +1 416 978 8528. E-mail address: bernard.schimmer@utoronto.ca (B.P. Schimmer). hormone (Clark et al., 2005; Coll et al., 2004). This trophic action involves the induction of genes with functions in steroidogene- sis, cell proliferation and cell structure as evidenced by studies in intact glands, isolated adrenal cells and adrenal cell lines (e.g., Imai et al., 1990; Simmonds et al., 2001; Rainey et al., 2004; Simpson and Waterman, 1988). Until the recent development of tools to assess the genome-wide actions of ACTH, however, most studies of ACTH action focused on the induction of tran- scripts with functions in steroidogenesis (Sewer and Waterman, 2001). We have used cDNA microarrays to identify the global effects of ACTH on transcript accumulation in the Y1 mouse 0303-7207/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2006.12.024