title: Circulating insulin-like factor 3 (INSL3) in healthy and infertile women.
abstract: OBJECTIVE
  How does insulin-like factor 3 (INSL3) concentration in blood vary across the menstrual cycle in women?
  
  
  CONCLUSIONS
  INSL3 is secreted by the theca interna cells of growing antral follicles and is phasic in its expression.
  
  
  BACKGROUND
  The relaxin-like hormone INSL3 is known to be expressed in follicles of several mammal species, and was recently shown in cows to be specifically secreted into the bloodstream by growing antral follicles, corresponding to follicular waves. In males INSL3 is known to be acutely independent of the hormones of the hypothalamic-pituitary-gonadal axis, suggesting that in women INSL3 might be a novel biomarker for antral follicle recruitment and development.
  
  
  METHODS
  Two cohorts of women were studied. First, 18 healthy women of reproductive age were followed longitudinally for one and a half cycles, with blood sampling and hormone measurement every 2-3 days. A second cohort comprised a cross-sectional study of 909 women attending an infertility clinic, with a single blood sample taken at entry, together with other clinical and hormonal parameters.
  
  
  METHODS
  Blood samples from both retrospective cohorts were analyzed for INSL3 using a highly sensitive time-resolved fluorescent immunoassay, and data were analyzed in comparison with other clinical and hormonal parameters.
  
  
  RESULTS
  For young healthy women of reproductive age, we showed a phasic expression of INSL3 corresponding to antral follicle growth in both the follicular and luteal phases of the cycle, which was significantly (P < 0.05) elevated compared with that during menses. For women attending an infertility clinic, those with diagnosed polycystic ovarian syndrome indicated significantly (P < 0.0005) greater circulating INSL3 levels and those with low ovarian reserve showed significantly (P < 0.002) decreased INSL3 values.
  
  
  CONCLUSIONS
  These were retrospective studies and the results were obtained from natural cycles only, with their inherent variability.
  
  
  CONCLUSIONS
  We show for the first time that INSL3 in women does vary across the menstrual cycle, and appears to reflect the number of growing antral follicles recruited within both follicular and luteal phases.
  
  
  BACKGROUND
  The present retrospective study was largely supported by departmental funds. There were no competing interests.
authors.affiliation: Leibniz Institute for Farm Animal Biology, 18196 Dummerstorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Anand-Ivell
authors.forename: K
authors.initials: K
authors.lastname: Tremellen
authors.forename: Y
authors.initials: Y
authors.lastname: Dai
authors.forename: K
authors.initials: K
authors.lastname: Heng
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: P G
authors.initials: PG
authors.lastname: Knight
authors.forename: G E
authors.initials: GE
authors.lastname: Hale
authors.forename: R
authors.initials: R
authors.lastname: Ivell
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000097:blood*; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D008597:Menstrual Cycle / Q000097:blood*; D006080:Ovarian Follicle / Q000254:growth & development; D010053:Ovary / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins
keywords: INSL3; PCOS; antral follicle; human ovary; menstrual cycle