Endocrine Abstracts

Context: Insulin-like peptide three (INSL3) is a testicular hormone, secreted by Leydig cells, during fetal life, in newborns, and after puberty. These 3 phases of testicular activation are impaired in CHH.

Objective: To evaluate in a single center circulating INSL3 in a significant series of men with CHH in order to asses the consequences of pre- and postnatal gonadotropin deficiency, to specify the INSL3 regulation by gonadotropins and to evaluate the potential diagnostic interest of this peptide.

Patients: Two hundred and sixty-eight CHH patients (77 untreated, 97 receiving testosterone and 94 under combined gonadotropin therapy (hCG and FSH)) and 40 age-matched normal men were evaluated.

Methods: Serum INSL3 was immunoassayed by a validated sensitive and specific RIA.

Results: Mean INSL3 levels (±S.D.) were 827±364 pg/ml in normal men and dramatically decreased (61±42 pg/ml; P<0.001) in untreated CHH patients, all of whom had values below controls. Positive correlations between both serum total testosterone (T) or LH and INSL3 (respectively P<0.01 and P<0.0001) were observed in untreated CHH. In T treated CHH mean INSL3 was also very low (50±25 pg/ml) but in CHH receiving combined hCG and FSH therapy, INSL3 was very significantly higher (402±292 pg/ml; P<0.001) than in untreated CHH. Combined FSH-hCG therapy (from 61±21 to 301±254 pg/ml) or hCG alone (from 48±10 to 223±114 pg/ml) significantly and prospectively increased INSL3 levels in CHH, contrary to T (from 61±21 to 53±37 pg/ml) or FSH monotherapies (from 48±10 to 60±16 pg/ml).

Conclusions: The dramatic INSL3 decrease in CHH is caused by LH deficiency and correlated with its severity. The increase in INSL3 levels during combined gonadotropin and hCG monotherapy reinforces its exclusive Leydigian origin and its positive regulation by LH/hCG. Finally, INSL3 seems as sensitive as total testosterone to evaluate the testicular Leydig function in CHH and is therefore a useful diagnostic marker.