Arachidonate 12-lipoxygenase in porcine anterior pituitary cells: its localization and possible function in gonadotrophs.
Arachidonate 12-lipoxygenase, which oxygenates positions 12 and 13 of arachidonic and linoleic acids, is present in porcine anterior pituitary cells. Colocalization of the 12-lipoxygenase with various pituitary hormones was examined by immunohistochemical double-staining using antibodies against 12-lipoxygenase and various anterior pituitary hormones. Under light microscopy, approximately 7% of the cells producing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were positive for 12-lipoxygenase, whereas the enzyme was detected in less than 2% of the cells producing thyrotrophin, prolactin, growth hormone (GH), and adrenocorticotrophin. In an attempt to examine the participation of 12-lipoxygenase metabolites in pituitary hormone release, we incubated the primary culture of porcine anterior pituitary cells with 12-hydroperoxy-arachidonic acid or 13-hydroperoxy-linoleic acid. Significant stimulation of LH and FSH release by these hydroperoxides was observed at 10 microM in a time-dependent manner. At doses around 10 microM these compounds produced responses of similar magnitude to 1 nM gonadotrophin-releasing hormone (GnRH), but higher concentrations (30 microM) of the compounds were required for GH release. In contrast, 12-hydroxy-arachidonic and 13-hydroxy-linoleic acids were almost ineffective. Furthermore, the gonadotrophin release by 1 nM GnRH was inhibited by nordihydroguaiaretic acid (a lipoxygenase inhibitor) with an IC50 of about 5 microM. Thus, the hydroperoxy (but not hydroxy) products of 12-lipoxygenase may be involved in the release of pituitary hormones especially LH and FSH.
Ikawa
H
H
Department of Obstetrics and Gynecology, Tokushima University, School of Medicine, Japan.
Yamamoto
K
K
Takahashi
Y
Y
Ueda
N
N
Hayashi
Y
Y
Yamamoto
S
S
Ishimura
K
K
Irahara
M
M
Aono
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001092:Arachidonate 12-Lipoxygenase / Q000032:analysis* / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D015289:Leukotrienes / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology; D008054:Lipid Peroxides; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013552:Swine / Q000378:metabolism*; D013997:Time Factors
D000991:Antithrombins; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008041:Linoleic Acids; D008054:Lipid Peroxides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D007987:Gonadotropin-Releasing Hormone; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D001092:Arachidonate 12-Lipoxygenase