title: Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome.
abstract: BACKGROUND
  Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development.
  
  
  OBJECTIVE
  The objective of the study was to characterize changes in INSL3 levels during spontaneous puberty in healthy boys, boys with aromatase inhibitor-induced hypergonadotropic hyperandrogenism, and boys with Leydig cell dysfunction.
  
  
  METHODS
  This was a prospective clinical study.
  
  
  METHODS
  The study was conducted at a university hospital pediatric endocrinology outpatient clinic.
  
  
  METHODS
  Patients included 30 healthy boys with idiopathic short stature (ISS) aged 9.0-14.5 yr and 14 boys with Klinefelter syndrome (KS) aged 10-13.9 yr.
  
  
  METHODS
  In ISS boys, intervention included aromatase inhibitor letrozole or placebo for 24 months.
  
  
  METHODS
  Serum INSL3 levels in relation to bone age, Tanner pubertal stages, and LH and testosterone levels were measured.
  
  
  RESULTS
  Onset of puberty was associated with a significant increase in INSL3 levels from 0.06 +/- 0.01 ng/ml at Tanner G1 to 0.32 +/- 0.16 ng/ml at G2 (P < 0.0001). Adult INSL3 levels (> or = 0.55 ng/ml) were attained at bone age 13-14 yr. ISS boys with letrozole-induced hypergonadotropic hyperandrogenism had, after 12 months of therapy, higher INSL3 levels than did placebo treated (0.85 +/- 0.54 vs. 0.26 +/- 0.17 ng/ml, P < 0.01). In KS boys during spontaneous puberty, after an initial increase similar to that in healthy boys, INSL3 concentrations leveled off despite hyperstimulation by LH. Positive correlations occurred between serum INSL3 and LH and between INSL3 and testosterone levels in all three groups (P < 0.0001).
  
  
  CONCLUSIONS
  In boys, the Leydig cell-specific hormone INSL3 may serve as a new marker for onset and progression of puberty. Pubertal increase in INSL3 levels seems to depend on LH. In KS subjects, INSL3 concentrations indicate Leydig cell dysfunction from midpuberty onward.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, FI-00029 Helsinki, Finland. anne.wikstrom@fimnet.fi
authors.forename: Anne M
authors.initials: AM
authors.lastname: Wikström
authors.forename: Katrine
authors.initials: K
authors.lastname: Bay
authors.forename: Matti
authors.initials: M
authors.lastname: Hero
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Andersson
authors.forename: Leo
authors.initials: L
authors.lastname: Dunkel
mesh_terms: D000293:Adolescent; D000365:Age Determination by Skeleton; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001827:Body Height / Q000187:drug effects; D002648:Child; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy; D006262:Health; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000139:chemically induced; D007265:Inhibins / Q000097:blood; D007328:Insulin / Q000097:blood*; D007713:Klinefelter Syndrome / Q000097:blood* / Q000188:drug therapy; D000077289:Letrozole; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009570:Nitriles / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D010919:Placebos; D011506:Proteins; D011627:Puberty / Q000097:blood*; D013223:Statistics as Topic; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D047072:Aromatase Inhibitors; D007328:Insulin; C084797:Leydig insulin-like protein; D009570:Nitriles; D010919:Placebos; D011506:Proteins; D014230:Triazoles; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D000077289:Letrozole; D007986:Luteinizing Hormone