scholarly journals Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig cells

Reproduction ◽  
2009 ◽  
Vol 138 (1) ◽  
pp. 163-175 ◽  
Author(s):  
María E Matzkin ◽  
Silvia I Gonzalez-Calvar ◽  
Artur Mayerhofer ◽  
Ricardo S Calandra ◽  
Mónica B Frungieri
Keyword(s):  
Sexual Development ◽  
Leydig Cells ◽  
Prostaglandin F2α ◽  
Mitogen Activated Protein Kinase ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Key Enzyme ◽  
Prostaglandin Endoperoxide Synthase ◽  
Regulatory Loop

We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF2α on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF2α. In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF2α production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF2α in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF2α inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

scholarly journals Role of Mitogen-Activated Protein Kinase Pathway in Prostaglandin F2α-Induced Rat Puerperal Uterine Contraction

Endocrinology ◽  
1997 ◽  
Vol 138 (8) ◽  
pp. 3103-3111 ◽  
Author(s):  
Masahide Ohmichi ◽  
Koji Koike ◽  
Akiko Kimura ◽  
Kanji Masuhara ◽  
Hiromasa Ikegami ◽  
...  
Keyword(s):  
Map Kinase ◽  
Uterine Contraction ◽  
Prostaglandin F2α ◽  
Mek Inhibitor ◽  
Biological Action ◽  
Mitogen Activated Protein Kinase ◽  
Myometrial Cells ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

Abstract In this study, prostaglandin (PG) F2α was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2α stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2α induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the β-adrenergic receptor kinase 1 (βARK1), which specifically blocks signaling mediated by the βγ subunits of G proteins, blocked the PGF2α-induced activation of MAP kinase. Ritodrine (1 μm), which is known to relax uterine muscle contraction, attenuated PGF2α-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2α-induced calcium mobilization, this inhibitor partially inhibited PGF2α-induced uterine contraction. These results provide evidence that PGF2α stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gβγ protein, suggesting that this new pathway may play an important role in the biological action of PGF2α on these cells.

scholarly journals Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades

2000 ◽  
Vol 352 (2) ◽  
pp. 419 ◽  
Author(s):  
Ann McGINTY ◽  
Marco FOSCHI ◽  
Yu-Wen E. CHANG ◽  
Jiahuai HAN ◽  
Michael J. DUNN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Prostaglandin Endoperoxide Synthase

scholarly journals Induction of prostaglandin endoperoxide synthase 2 by mitogen-activated protein kinase cascades

2000 ◽  
Vol 352 (2) ◽  
pp. 419-424 ◽  
Author(s):  
Ann MCGINTY ◽  
Marco FOSCHI ◽  
Yu-Wen E. CHANG ◽  
Jiahuai HAN ◽  
Michael J. DUNN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Inflammatory Diseases ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Diverse Range ◽  
Adenoviral Infection ◽  
Prostaglandin Endoperoxide ◽  
Mitogen Activated Protein ◽  
Prostaglandin Endoperoxide Synthase

Prostaglandin endoperoxide synthase (PGHS) catalyses the rate-limiting step in the formation of prostaglandin and thromboxane eicosanoids from arachidonic acid released by phospholipase A2. Two forms of PGHS exist, PGHS-1 and PGHS-2. PGHS-2, normally absent from cells, is rapidly expressed in response to a wide variety of stimuli and has been implicated in the pathogenesis of colon cancer and several inflammatory diseases. The three principal mitogen-activated protein kinase (MAPK) pathways are the extracellular signal-regulated protein kinase (ERK), the c-Jun N-terminal kinase (JNK) cascade and the p38-MAPK cascade. The present study was undertaken to investigate the putative involvement of the MAPK cascades in PGHS-2 induction. The potential role of ERK in PGHS-2 up-regulation was assessed by using cell lines expressing, both stably and after adenoviral infection, constitutively active forms of its upstream activator MAPK/ERK kinase (MEK1). The possible involvement of JNK and p38-MAPK in positively modulating PGHS-2 transcription was investigated by using adenovirus-mediated transfer of active forms of their respective specific upstream kinases, mitogen-activated protein kinase kinase (MKK) 7 and MKK3/MKK6. ERK activation promoted the induction of PGHS-2 mRNA and protein. Similarly, activation of JNK by Ad-MKK7D and p38-MAPK by Ad-MKK3bE/Ad-MKK6bE resulted in the increased expression of PGHS-2. These results provide evidence that activation of all three of the major mammalian MAPK leads to the induction of PGHS-2 mRNA and protein. Because PGHS-2 is up-regulated by a diverse range of stimuli, both mitogenic and stress-evoking, these results provide evidence that the convergence point of these stimuli could be the activation of one or more MAPK cascade(s).

scholarly journals Differential Role of Threonine and Tyrosine Phosphorylation in the Activation and Activity of the Yeast MAPK Slt2

2021 ◽  
Vol 22 (3) ◽  
pp. 1110
Author(s):  
Gema González-Rubio ◽  
Ángela Sellers-Moya ◽  
Humberto Martín ◽  
María Molina
Keyword(s):  
Cell Wall ◽  
Biological Activity ◽  
Biological Significance ◽  
Mitogen Activated Protein Kinase ◽  
Activation Loop ◽  
High Increase ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Full Activation

The Mitogen-Activated Protein Kinase (MAPK) Slt2 is central to signaling through the yeast Cell Wall Integrity (CWI) pathway. MAPKs are regulated by phosphorylation at both the threonine and tyrosine of the conserved TXY motif within the activation loop (T190/Y192 in Slt2). Since phosphorylation at both sites results in the full activation of MAPKs, signaling through MAPK pathways is monitored with antibodies that detect dually phosphorylated forms. However, most of these antibodies also recognize monophosphorylated species, whose relative abundance and functionality are diverse. By using different phosphospecific antibodies and phosphate-affinity (Phos-tag) analysis on distinct Slt2 mutants, we determined that Y192- and T190-monophosphorylated species coexist with biphosphorylated Slt2, although most of the Slt2 pool remains unphosphorylated following stress. Among the monophosphorylated forms, only T190 exhibited biological activity. Upon stimulation, Slt2 is first phosphorylated at Y192, mainly by the MAPKK Mkk1, and this phosphorylation is important for the subsequent T190 phosphorylation. Similarly, dephosphorylation of Slt2 by the Dual Specificity Phosphatase (DSP) Msg5 is ordered, with dephosphorylation of T190 depending on previous Y192 dephosphorylation. Whereas Y192 phosphorylation enhances the Slt2 catalytic activity, T190 is essential for this activity. The conserved T195 residue is also critical for Slt2 functionality. Mutations that abolish the activity of Slt2 result in a high increase in inactive Y192-monophosphorylated Slt2. The coexistence of different Slt2 phosphoforms with diverse biological significance highlights the importance of the precise detection of the Slt2 phosphorylation status.

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