title: The loss of luteal progesterone production in women is associated with a galectin switch via α2,6-sialylation of glycoconjugates.
abstract: BACKGROUND
  Luteal progesterone is fundamental for reproduction, but the molecular regulation of the corpus luteum (CL) in women remains unclear. Galectin-1 and galectin-3 bind to the sugar chains on cells to control key biological processes including cell function and fate.
  
  
  METHODS
  The expression and localization of LGALS1 and LGALS3 were analyzed by quantitative PCR and histochemical analysis, with special reference to α2,6-sialylation of glycoconjugates in carefully dated human CL collected across the menstrual cycle and after exposure to human chorionic gonadotrophin (hCG) in vivo. The effects of hCG and prostaglandin E2 on the expression of galectins and an α2,6-sialyltransferase 1 (ST6GAL1) in granulosa lutein cells were analyzed in vitro.
  
  
  RESULTS
  Galectin-1 was predominantly localized to healthy granulosa lutein cells and galectin-3 was localized to macrophages and regressing granulosa lutein cells. Acute exposure to luteotrophic hormones (hCG and prostaglandin E2) up-regulated LGALS1 expression (P < .001). ST6GAL1, which catalyzes α2,6-sialylation to block galectin-1 binding, increased during luteolysis (P < .05) as did LGALS3 (P < .05). Luteotrophic hormones reduced ST6GAL1 and LGALS3 in vivo (P < .05) and in vitro (P < .001). There was an inverse correlation between the expression of ST6GAL1 and HSD3B1 (P < .01) and a distinct cellular relationship among α2,6-sialylation, 3β-hydroxysteroid dehydrogenase, and galectin expression.
  
  
  CONCLUSIONS
  Galectin-1 is a luteotrophic factor whose binding is inhibited by α2,6-sialylation in the human CL during luteolysis. ST6GAL1 and galectin-3 expression is increased during luteolysis and associated with a loss of progesterone synthesis. Luteotrophic hormones differentially regulate galectin-1 and galectin-3/α2,6-sialylation in granulosa lutein cells, suggesting a novel galectin switch regulated by luteotrophic stimuli during luteolysis and luteal rescue.
authors.affiliation: Medical Research Council Centre for Reproductive Health (J.N.-K., L.B., W.C.D.), The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Creative Research Institution (M.A.), Hokkaido University, Sapporo 001-0021, Japan; and Laboratory of Histology and Cytology (J.N.-K., T.I.), Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nio-Kobayashi
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Boswell
authors.forename: Maho
authors.initials: M
authors.lastname: Amano
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000378:metabolism*; D005260:Female; D037483:Galectin 1 / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism*; D006801:Humans; D003341:Luteolysis; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*
chemical_list: D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; D006001:Glycoconjugates; D011374:Progesterone; D019158:N-Acetylneuraminic Acid