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Changes in Serum Insulin-Like Factor 3 during Normal Male Puberty

Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation (A.F., A.G., C.F.), and Department of Pediatrics (F.R., L.R.C.), University of Padova, 35121 Padova, Italy; and Department of Medical Pathophysiology (A.L.), University of Rome "La Sapienza", 00100 Rome, Italy

Address all correspondence and requests for reprints to: Prof. Carlo Foresta, University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova, Italy. E-mail: carlo.foresta{at}unipd.it.

Context: Insulin-like factor 3 (INSL3) is produced by the Leydig cells, and in adults, its secretion is dependent on the state of differentiation of these cells, which, in turn, is dependent on LH. However, the secretion and regulation of INSL3 during puberty is unknown.

Objective: Our objective was to evaluate INSL3 concentrations during normal male puberty and the relation of INSL3 to LH, FSH, and testosterone.

Design and Setting: We conducted a cross-sectional study from January to December 2005 at academic clinics.

Patients: Participating in the study were 75 healthy male subjects aged 9.5–17.5 yr, homogeneously distributed into five pubertal groups of 15 according to Tanner stages.

Main Outcome Measures: We assessed mean testicular volume and LH, FSH, testosterone, and INSL3 concentrations in relation to age and pubertal stage.

Results: We observed an increase of INSL3 and LH levels from Tanner stage 2 to 4, and an increase of FSH from stage 2 to 3. Testosterone levels increased from stage 3 to 4. No differences were seen for all measured hormones between stages 4 and 5. The increase in INSL3 seemed therefore to anticipate the increase in testosterone. However, INSL3 plasma concentrations at pubertal stages 4 and 5 are about one fourth of adult levels, whereas FSH, LH, and testosterone reached adult levels by stage 4. Positive significant correlations were found between INSL3 and LH for all pubertal stages.

Conclusions: This study provides information on the physiological dynamics of INSL3, showing that the serum concentrations of this hormone increased progressively throughout puberty under the differentiating action of LH on Leydig cells. INSL3 is therefore confirmed to represent a marker of Leydig cell differentiation and function. However, a prolonged exposure to LH seems to be necessary to reach INSL3 concentrations of adults. A possible use of INSL3 in puberty disorders is promising.

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