title: Normal insulin-like peptide-3 levels despite low testosterone in adult males with Prader-Willi syndrome: variations in Leydig cell function from infancy through adulthood.
abstract: BACKGROUND
  Cryptorchidism, incomplete pubertal development, and low testosterone are manifestations of hypogonadism in Prader-Willi syndrome (PWS). Insulin-like peptide-3 (INSL3) facilitates testicular descent in the fetus and reflects Leydig cell number in adults. INSL3 levels in PWS have not been previously reported.
  
  
  OBJECTIVE
  The objectives of the study were to characterize the age-related changes in INSL3 in PWS males and correlate INSL3 with unilateral vs. bilateral cryptorchidism, body mass index, gonadotropins, testosterone, anti-mullerian hormone (AMH), and inhibin B.
  
  
  METHODS
  We measured INSL3, LH, FSH, testosterone, AMH, and inhibin B in 40 PWS males (23 deletion, 17 uniparental disomy) aged 2 months to 36 yr. Control samples for INSL3 were obtained from 365 normal males, aged 1 d to 36 yr.
  
  
  RESULTS
  INSL3 levels (mean and range) for PWS age groups younger than 6 months, 0.5-10.0 yr, 10.1-19.0 yr, and older than 19.0 yr were 217 (68-380), 42 (16-112), 390 (16-1028), and 642 (290-964) pg/ml, respectively, and did not differ significantly from values for normal males. In seven of 14 boys aged 10.1-19 yr, INSL3, testosterone, and LH were low (37.4 ± 19.4 pg/ml, 1.44 ± 0.46 nmol/liter, 0.3 ± 0.6 IU/liter). The other seven with higher INSL3, testosterone, and LH (693.1 ± 305.8 pg/ml, 5.91 ± 2.77 nmol/liter, 2.7 ±1.9 IU/liter) had more advanced pubertal development. INSL3 was normal in seven of nine males aged older than 19 yr, despite low testosterone in six. After controlling for age, INSL3 correlated with LH (P = 0.005) and testosterone (P < 0.001) but not with FSH, AMH, or inhibin B.
  
  
  CONCLUSIONS
  Most PWS males have normal INSL3 levels. By contrast, testosterone levels after infancy are low. These findings suggest a specific defect in Leydig cell function.
authors.affiliation: Neuropediatrics Unit, Department of Pediatrics, Shaare Zedek Medical Center, the Hebrew University, Jerusalem 91031, Israel. hirschmd@gmail.com
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Hirsch
authors.forename: Talia
authors.initials: T
authors.lastname: Eldar-Geva
authors.forename: Varda
authors.initials: V
authors.lastname: Gross-Tsur
authors.forename: Fortu
authors.initials: F
authors.lastname: Benarroch
authors.forename: Marc
authors.initials: M
authors.lastname: Roger
authors.forename: Najiba
authors.initials: N
authors.lastname: Lahlou
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000503:physiopathology*; D011506:Proteins / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D013739:Testosterone