Protein tyrosine phosphatases regulate arachidonic acid release, StAR induction and steroidogenesis acting on a hormone-dependent arachidonic acid-preferring acyl-CoA synthetase.
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 steroidogenesis.
Cano
Florencia
F
Department of Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155, 5th, Buenos Aires C1121ABG, Argentina.
Poderoso
Cecilia
C
Cornejo Maciel
Fabiana
F
Castilla
Rocío
R
Maloberti
Paula
P
Castillo
Fernanda
F
Neuman
Isabel
I
Paz
Cristina
C
Podestá
Ernesto J
EJ
D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003066:Coenzyme A Ligases / Q000378:metabolism*; D007984:Leydig Cell Tumor; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*
D026901:Membrane Transport Proteins; D016718:Arachidonic Acid; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D017027:Protein Tyrosine Phosphatases; D003066:Coenzyme A Ligases