The enzymes in cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism in human corpora lutea: dependence on luteal phase, cellular and subcellular distribution.
Eicosanoids synthesized within corpus luteum are presumed to regulate luteal function in women. However, the potential cellular source(s) of the eicosanoids, whether small and large luteal cells differ in eicosanoid synthesis and whether eicosanoids other than prostaglandin (PG)E2, PGF2 alpha and 6-keto-PGI1 alpha can be synthesized, have not been investigated. The present immunocytochemical studies were undertaken to answer these questions using mono and polyclonal antibodies to several enzymes in arachidonic acid metabolism by cyclooxygenase and lipoxygenase pathways. Human corpora lutea from early (n = 5), mid (n = 6) and late (n = 3) luteal phases were specifically immunostained for all the enzymes. All the enzymes were present in small and large luteal cells as well as in non luteal cells. However, small luteal cells contained more immunoreactive 5-lipoxygenase, PGD2 and PGF2 alpha synthases; large luteal cells contained more TXA2 synthase and 12-lipoxygenase; small and large luteal cells contained similar amounts of cyclooxygenase and PGI2 synthase. In all the cells, immunoreactive PGD2, PGI2 and TXA2 synthases increased from early to mid luteal phase and then declined in late luteal phase. Cyclooxygenase, 5- and 12-lipoxygenases and PGF2 alpha synthase, on the other hand, increased from early to mid and mid to late luteal phases. Immunoreactive cyclooxygenase and 5- and 12-lipoxygenases were present primarily in rough endoplasmic reticulum (ER) and/or smooth ER and cytoplasm. Quite unexpectedly, all three enzymes were also found in nuclear membranes, condensed chromatin and especially at the perimeter of condensed chromatin. Dispersed chromatin contained very little or no immunoreactive enzyme. These results indicate that regulation of human luteal function by eicosanoids synthesized within the corpus luteum is complex involving perhaps a) small and large luteal as well as non luteal cells, b) eicosanoids which have not been previously considered to play a role in luteal function and c) coordinate regulation of more than one enzyme in the pathways of arachidonic acid metabolism.
Mitchell
D E
DE
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30303.
Lei
Z M
ZM
Rao
C V
CV
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001092:Arachidonate 12-Lipoxygenase / Q000032:analysis*; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000201:enzymology; D003338:Corpus Luteum / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D015777:Eicosanoids / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000032:analysis*; D054834:Lipocalins; D008597:Menstrual Cycle; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D013930:Thromboxane-A Synthase / Q000032:analysis*
D000911:Antibodies, Monoclonal; D001095:Arachidonic Acids; D002843:Chromatin; D015777:Eicosanoids; D054834:Lipocalins; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase