title: Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels.
abstract: OBJECTIVE
  To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge.
  
  
  METHODS
  ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4).
  
  
  METHODS
  Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles.
  
  
  RESULTS
  A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles.
  
  
  CONCLUSIONS
  The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.
authors: Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark.
authors: Jane Alrø
authors: JA
authors: Bøtkjær
authors: Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark.
authors: Janni Vikkelsø
authors: JV
authors: Jeppesen
authors: Holbæk Fertility Clinic, Holbæk, Denmark.
authors: Marie Louise
authors: ML
authors: Wissing
authors: Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark.
authors: Søren
authors: S
authors: Kløverpris
authors: Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark.
authors: Claus
authors: C
authors: Oxvig
authors: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors: J Ian
authors: JI
authors: Mason
authors: Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark.
authors: Tanni
authors: T
authors: Borgbo
authors: Laboratory of Reproductive Biology, Juliane Marie Center for Women, Children, and Reproduction, Copenhagen University Hospital, Copenhagen University, Copenhagen, Denmark. Electronic address: yding@rh.dk.
authors: Claus Yding
authors: CY
authors: Andersen
mesh_terms: D000735:Androstenedione / Q000378:metabolism; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000201:enzymology*; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D008597:Menstrual Cycle / Q000378:metabolism; D006080:Ovarian Follicle / Q000201:enzymology*; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D013739:Testosterone / Q000378:metabolism
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D001141:Aromatase; C561410:CYP19A1 protein, human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: AMH; PAPP-A; aromatase; human follicles; human ovarian steroidogenesis