title: LOX-1 regulates estrogenesis via intracellular calcium release from bovine granulosa cells.
abstract: Estradiol produced by ovarian granulosa cells triggers the luteinizing hormone surge which in turn initiates ovulation in female mammals. Disturbances in estradiol production from granulosa cells are a major reason for reproductive dysfunctions in dairy cows. Endogenous estradiol production might be altered by reactive oxygen species (ROS) such as oxidized low-density lipoprotein (ox-LDL). Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a receptor of ox-LDL, leads to increased estrogenesis in granulosa cells. This activity is mediated by calcium release from endoplasmic reticulum (ER)-dependent and ER-independent calcium pools. Inhibition of the LOX-1 signal transduction pathway is followed by mitochondrial alterations. The membrane potential ΔΨ increases and the ROS production decreases in mitochondria after blocking LOX-1. Our data indicate that blocking the LOX-1 receptor signal pathway might be a promising way to improve steroid hormone concentrations in metabolically highly active female mammals and, therefore, to defend against reproductive dysfunctions in humans and animals.
authors.affiliation: Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Weitzel
authors.forename: A
authors.initials: A
authors.lastname: Vernunft
authors.forename: B
authors.initials: B
authors.lastname: Krüger
authors.forename: C
authors.initials: C
authors.lastname: Plinski
authors.forename: T
authors.initials: T
authors.lastname: Viergutz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D010060:Ovulation / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D004958:Estradiol; D007986:Luteinizing Hormone; D002118:Calcium
keywords: female cycle; follicular dysfunction; reproductive fitness; steroidogenesis