Insulin-like factor 3 levels in cord blood and serum from children: Effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism

Context: The Leydig cell hormone insulin- like factor 3 ( INSL3) is important for testicular descent. Currently INSL3 levels in cord blood, in serum throughout childhood, and in relation to congenital cryptorchidism are unknown. Objective: The objective of the study was to characterize INSL3 levels in cord blood during the postnatal activation of the hypothalamic-pituitary- gonadal axis and in later childhood in normal boys and girls and cryptorchid boys. Design and Participants: Serum from 267 3- month- old boys of a prospective study with standardized cryptorchidism classification was analyzed for INSL3 ( of these, 99 also had cord blood samples). Testicular position was known in 151 controls and 54 transiently cryptorchid and 62 persistently cryptorchid subjects. Eight infant girls, 26 boys ( 4.1 - 10.1 yr), and 13 girls ( 3.7 - 8.7 yr) were also included. Outcome Measure: INSL3, age, testicular position, LH, and testosterone were measured. Results: INSL3 levels were significantly higher ( P < 0.001) in cord blood and 3- month- old boys as compared with older prepubertal boys. At 3 months of age, INSL3 correlated significantly with LH in healthy boys. Cord blood INSL3 was significantly reduced in persistently cryptorchid boys ( P = 0.001), and 3- month- old persistently cryptorchid boys had a significantly increased LH to INSL3 ratio ( P = 0.014). INSL3 was unmeasurable in girls at all ages. Conclusions: In boys, early postnatal INSL3 is markedly higher as compared with later childhood, presumably because it is stimulated by the transient postnatal LH peak. INSL3 was unmeasurable in girls at all ages. Reduced cord blood INSL3 and an increased LH to INSL3 ratio at 3 months of age in persistently cryptorchid boys suggest impaired Leydig cell function in cryptorchid boys already in the perinatal period.