Serum INSL3 dynamics in young men with congenital hypogonadotropic hypogonadism treated with gonadotropins
Giuseppe Bellastella, Dario Esposito, Luigi Maione, Daniela Visconti, Vincenzo Palumbo, Annamaria De Bellis, Antonio Bellastella & Antonio Agostino Sinisi
Insulin-like factor 3 (INSL3) is produced by Leydig cells. In boys, the levels of INSL3 rise at pubertal stage P2 and further increase throughout puberty in close correlation with T and LH concentrations. In men with hypogonadotropic hypogonadism (HH) INSL3 levels have been found very low and increased after short-term hCG treatment. Whether FSH plays a role in regulating INSL3 secretion is questioned. Aim of this study was to evaluate serum INSL3 levels during long-term hCG and rFH+hCG replacement therapy in men with HH.
Methods: Eighteen men (1824 years old) with never treated prepubertal-onset HH received 2000 IU i.m. hCG to induce puberty. After 612 months, they were treated with hCG plus rFSH (75 IU) twice a week. Serum INSL3 levels were assessed at diagnosis and every 3 months throughout gonadotropin replacement therapy.
Results: INSL3 levels, low at diagnosis (33.3±5.4 pg/ml), significantly rose to 453±53.1 (P<0.001) after 612 months of hCG alone, when near all patients reached pubertal stage P3. A further significant increase was observed after 3 and 6 months of rFSH+hCG administration (532.5±56.3 and 601.2±58.1, respectively, P<0.040.07).
Conclusions: INSL3 concentration increases progressively under hCG therapy paralleling the pubertal changes induced in men with HH. A further rise of INSL3 levels during the combined rFSH and hCG administration suggest a positive effect of FSH on Leydig cell secretion.