An adrenocorticotropin-regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl-CoA thioesterase enzyme

Carla Finkielstein, Paula Maloberti, Carlos F. Mendez, Cristina Paz, Fabiana Cornejo Maciel, Cora Cymeryng, Isabel Neuman, Laura Dada, Pablo G. Mele, Angela Solano, Ernesto J. Podestá*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

We have previously reported the purification of a phosphoprotein (p43) intermediary in steroid synthesis from adrenal zona fasciculata [Paz C., Dada, L.A., Cornejo Maciel, M.F., Mele, P.G., Cymeryng, C.B., Neuman, I., Mendez, C.F., Finkielstein, C.V., Solano, A.R., Park, M., Fischer, W.H., Towbin, H., Scartazzini, R. and Podesta, E.J. (1994) Eur. J. Biochem. 224, 709-716]. Here, we describe the cloning and sequencing of a cDNA encoding p43 as well as the hormonal regulation of the p43 transcript. The protein resulted homologous to a very recently described mitochondrial peroxisome-proliferator-induced very-long-chain acyl-CoA thioesterase (MTE-I). The deduced amino acid sequence of the protein shows consensus sites for phosphorylation by different protein kinases, and a lipase serine motif. Antibodies raised against a synthetic peptide that includes the lipase serine motif and against the N-terminal region of p43 block the action of the protein. The transcript of p43 was detected in ovary of pseudopregnant rats, rat adrenal zona fasciculata and glomerulosa, mouse Leydig tumor cell line (MA-10), rat brain and human placenta. Inhibition of adrenocorticotropin hormone (ACTH) release and steroid synthesis by by dexamethasone produced a dose-dependent decrease in the abundance of the adrenal transcript. The transcript was induced by in vivo stimulation of the adrenals with ACTH. The effect bad a rapid onset (5 min), reached maximal stimulation (62%) at 15 min, and returned to basal levels at 30 min. The effect of ACTH on the p43 transcript was inhibited by actinomycin D and enhanced by cycloheximide. Our results provide the first evidence linking acyl-CoA thioesterases with very-long-chain specificities, and a protein intermediary in steroid synthesis, thereby supporting a regulatory role for acyl-CoA thioesterases in steroidogenic tissues.

Original languageEnglish (US)
Pages (from-to)60-66
Number of pages7
JournalEuropean Journal of Biochemistry
Volume256
Issue number1
DOIs
StatePublished - Aug 15 1998

Keywords

  • Acyl-CoA thioesterase
  • Arachidonic acid
  • Hormone
  • Phosphorylation
  • Steroidogenesis

ASJC Scopus subject areas

  • Biochemistry

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