Protein tyrosine phosphatases regulate arachidonic acid release, StAR induction and steroidogenesis acting on a hormone-dependent arachidonic acid-preferring acyl-CoA synthetase

The Journal of Steroid Biochemistry and Molecular Biology
Florencia CanoE J Podestá

Abstract

The activation of the rate-limiting step in steroid biosynthesis, that is the transport of cholesterol into the mitochondria, is dependent on PKA-mediated events triggered by hormones like ACTH and LH. Two of such events are the protein tyrosine dephosphorylation mediated by protein tyrosine phosphatases (PTPs) and the release of arachidonic acid (AA) mediated by two enzymes, ACS4 (acyl-CoA synthetase 4) and Acot2 (mitochondrial thioesterase). ACTH and LH regulate the activity of PTPs and Acot2 and promote the induction of ACS4. Here we analyzed the involvement of PTPs on the expression of ACS4. We found that two PTP inhibitors, acting through different mechanisms, are both able to abrogate the hormonal effect on ACS4 induction. PTP inhibitors also reduce the effect of cAMP on steroidogenesis and on the level of StAR protein, which facilitates the access of cholesterol into the mitochondria. Moreover, our results indicate that exogenous AA is able to overcome the inhibition produced by PTP inhibitors on StAR protein level and steroidogenesis. Then, here we describe a link between PTP activity and AA release, since ACS4 induction is under the control of PTP activity, being a key event for AA release, StAR induction and steroidog...Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M J KangT T Yamamoto
Aug 17, 2005·Journal of Lipid Research·Mary C HuntStefan E H Alexson

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Citations

Sep 10, 2011·Journal of Lipid Research·Mariana CookeFabiana Cornejo Maciel
Jan 9, 2007·Molecular and Cellular Endocrinology·Alejandra GorostizagaCristina Paz
Feb 5, 2013·Molecular and Cellular Endocrinology·Ulises OrlandoPaula Maloberti
Apr 12, 2016·Frontiers in Endocrinology·Carmen Ruggiero, Enzo Lalli
Dec 30, 2014·Molecular and Cellular Endocrinology·Ana F CastilloErnesto J Podesta

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