Arachidonic acid and lipoxygenase products stimulate gonadotropin alpha-subunit mRNA levels in pituitary alpha T3-1 cell line: role in gonadotropin releasing hormone action. 1994

D Ben-Menahem, and Z Shraga-Levine, and R Limor, and Z Naor
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Ramat Aviv, Israel.

The role of arachidonic acid (AA) and its lipoxygenase metabolites in gonadotropin releasing hormone (GnRH) induced alpha-subunit gene expression was investigated in the transformed gonadotroph cell line alpha T3-1. The stable analog [D-Trp6]GnRH (GnRHa) stimulated [3H]AA release from prelabeled cells after a lag of 1-2 min. Addition of AA stimulated alpha-subunit mRNA levels in a dose-dependent manner, a significant effect being detected at 5 microM AA. Among various lipoxygenase metabolites of AA, only the 5-lipoxygenase products 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C4 (LTC4) stimulated alpha-subunit mRNA levels. However, while 5-HETE and LTC4 (0.1 nM each) were active already after 30 min of incubation, similar to GnRHa, AA (20 microM) stimulated alpha-mRNA levels after 1 h of incubation. Addition of the phospholipase A2 inhibitor 4-bromophenacyl bromide (BPB) or the selective 5-lipoxygenase inhibitor L-656,224 inhibited GnRHa elevation of alpha-subunit mRNA by 65%, while the cyclooxygenase inhibitor indomethacin had no effect. Addition of AA (20 microM) or LTC4 (0.1 nM) to normal cultured rat pituitary cells mimicked the rapid (30 min) stimulatory effect of GnRH (1 nM) upon alpha-subunit, LH beta, and FSH beta mRNA levels, while 5-HETE (0.1 nM) stimulated only FSH beta mRNA levels at this time point. Thus AA and selected 5-lipoxygenase products, in particular LTC4, participate in GnRHa-induced alpha-subunit mRNA elevation.

UI MeSH Term Description Entries
D008084 Lipoxygenase An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Lipoxidase,Linoleate-Oxygen Oxidoreductase,Lipoxygenase-1,Lipoxygenase-2,Linoleate Oxygen Oxidoreductase,Lipoxygenase 1,Lipoxygenase 2,Oxidoreductase, Linoleate-Oxygen
D008297 Male Males
D010902 Pituitary Gland A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM. Hypophysis,Hypothalamus, Infundibular,Infundibular Stalk,Infundibular Stem,Infundibulum (Hypophysis),Infundibulum, Hypophyseal,Pituitary Stalk,Hypophyseal Infundibulum,Hypophyseal Stalk,Hypophysis Cerebri,Infundibulum,Cerebri, Hypophysis,Cerebrus, Hypophysis,Gland, Pituitary,Glands, Pituitary,Hypophyseal Stalks,Hypophyses,Hypophysis Cerebrus,Infundibular Hypothalamus,Infundibular Stalks,Infundibulums,Pituitary Glands,Pituitary Stalks,Stalk, Hypophyseal,Stalk, Infundibular,Stalks, Hypophyseal,Stalks, Infundibular
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006893 Hydroxyeicosatetraenoic Acids Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes. HETE,Acids, Hydroxyeicosatetraenoic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001094 Arachidonate 5-Lipoxygenase An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes. 5-Lipoxygenase,Arachidonic Acid 5-Lipoxygenase,LTA4 Synthase,Leukotriene A Synthase,Leukotriene A4 Synthase,Leukotriene A4 Synthetase,5 Lipoxygenase,5-Lipoxygenase, Arachidonate,5-Lipoxygenase, Arachidonic Acid,Arachidonate 5 Lipoxygenase,Arachidonic Acid 5 Lipoxygenase,Synthase, LTA4,Synthase, Leukotriene A,Synthase, Leukotriene A4,Synthetase, Leukotriene A4
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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