title: Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.
abstract: BACKGROUND
  Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy.
  
  
  OBJECTIVE
  Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells.
  
  
  METHODS
  Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center.
  
  
  METHODS
  Patients were anonymous oocyte donors.
  
  
  METHODS
  Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa).
  
  
  METHODS
  P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits.
  
  
  RESULTS
  Both total hCG (P = 0.0003) and purified standard hCG (P < 0.0001) stimulated a dose-dependent increase in P4 production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant).
  
  
  CONCLUSIONS
  Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.
authors: Division of Reproductive Endocrinology and Fertility and Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27713, USA.
authors: John R
authors: JR
authors: Crochet
authors: Anish A
authors: AA
authors: Shah
authors: David W
authors: DW
authors: Schomberg
authors: Thomas M
authors: TM
authors: Price
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005470:Fluorometry; D006031:Glycosylation; D006801:Humans; D007536:Isomerism; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D034461:Luteinization / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*
chemical_list: D006063:Chorionic Gonadotropin; D011374:Progesterone