title: Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells.
abstract: Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFRs) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized in the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production in luteal cells obtained at mid-late and late luteal phases, but did not decrease progesterone production by granulosa cells or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.
authors: Department of Physiological SciencesEastern Virginia Medical School, Norfolk, Virginia 23501, USA.
authors: Soon Ok
authors: SO
authors: Kim
authors: Department of Physiological SciencesEastern Virginia Medical School, Norfolk, Virginia 23501, USA.
authors: Nune
authors: N
authors: Markosyan
authors: Department of Physiological SciencesEastern Virginia Medical School, Norfolk, Virginia 23501, USA.
authors: Gerald J
authors: GJ
authors: Pepe
authors: Department of Physiological SciencesEastern Virginia Medical School, Norfolk, Virginia 23501, USA duffydm@evms.edu.
authors: Diane M
authors: DM
authors: Duffy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003341:Luteolysis / Q000187:drug effects / Q000502:physiology*; D008252:Macaca fascicularis; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D011374:Progesterone; D015237:Dinoprost