title: Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls.
abstract: OBJECTIVE
  To elucidate the natural course of circulating insulin-like peptide 3 (INSL3) levels according to puberty as well as its relation to other reproductive hormones.
  
  
  METHODS
  Population-based cohort study.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Healthy peripubertal girls (n = 10) examined every 6 months; total number of examinations was 84; median (range) per girl: 9 (4-10), including staging of pubertal breast development and blood samples.
  
  
  METHODS
  None.
  
  
  METHODS
  Serum levels of INSL3, inhibin B, E2, antimüllerian hormone, LH, and FSH (validated immunoassays), and T and androstenedione (liquid chromatography-tandem mass spectrometry).
  
  
  RESULTS
  Serum levels of INSL3 varied considerably between girls (range, 0.01-0.27 ng/mL) and within each girl as puberty progressed; intraindividual variation, median (range) 102% (65%-143%). Insulin-like peptide 3 increased in late puberty (B1 to B4+B5); geometric mean 0.03 ng/mL to 0.15 ng/mL. Insulin-like peptide 3 levels reflected markers of large follicles (T, androstendione, inhibin B, and E2) better than markers of small follicles (antimüllerian hormone), and INSL3 staining was localized in theca interna cells of antral follicles.
  
  
  CONCLUSIONS
  Insulin-like peptide 3 increased in late puberty, albeit inter- and intraindividual variations were substantial. Immunohistochemistry and intraindividual variation, as well as relations to other ovarian hormones, reveal that INSL3 in girls is a unique and specific marker of theca cells surrounding antral follicles. The potential clinical use of INSL3 for evaluation of ovarian function in girls remains to be elucidated.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: casperhagen@gmail.com.
authors.forename: Casper P
authors.initials: CP
authors.lastname: Hagen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel G
authors.initials: MG
authors.lastname: Mieritz
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: John E
authors.initials: JE
authors.lastname: Nielsen
authors.affiliation: School of Biosciences, The University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Anand-Ivell
authors.affiliation: School of Biosciences, The University of Nottingham, Nottingham, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Ivell
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D005260:Female; D006262:Health; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D008137:Longitudinal Studies; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D011627:Puberty / Q000097:blood*; D013799:Theca Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins
keywords: INSL3; follicle; girl; puberty; theca