O-047. Signal transduction by growth hormone through Stat 5 is modulated by arachidonic acid

L. Fernández, D. Sliva, O. Lahuna, L. A. Haldosén, G. Norstedt, A. Mode, Jan-Ake Gustafsson

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GH stimulation of various cell lines induces binding of nuclear proteins to DNA elements present in the promoter region of Serine Protease Inhibitor (SPI) gene 2.1. GH-dependent activation of the latent transcription factor Stat 5 and of PLA2 has been described. Arachidonic acid (M) has been implicated in GH signalling pathways affecting gene transcription. Here we have investigated the possibility of an interplay between Stat 5 and M signalling pathways. Nuclear extracts obtained from BRL-4 cells cultured in the presence or absence of GH in combination with various inhibitors of M metabolism or inhibitors of phospholipase activity were used in electromobility shift assays with the SPI 2.1 Stat 5 response element SPIGLE1. Inhibitor's of M lipoxygenase (LOX) metabolism reduced GH-activated Stat 5 binding to SPIGLE1 while inhibition of cyclooxygenase (COX) metabolism had no effect. Quantification of the relative amounts of GH induced Stat 5 binding activity in cellular extracts treated with SKF 525A, a monooxygenase (EPOX) inhibitor, showed a 2-fold amplification of the activation compared with GH treatment alone. ETYA, an inhibitor of COX-, LOX- and EPOX- catalysed metabolism of M, inhibited GH-induced Stat 5 binding by 50%. Addition of M to serum-starved cells induced Stat 5 binding to SPIGLE1 but less efficiently than GH. Furthermore, mepacrine, a non-selective inhibitor of PLA2 reduced GH activated Stat 5 binding whereas inhibitors of PLC had no effect. These results suggest that a metabolite(s) of M can modulate GH induced Stat 5 activation.

Original languageEnglish (US)
Number of pages1
JournalEndocrinology and Metabolism, Supplement
Issue numberA
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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