• PMID: 24243640
• Gene Name: INSL3
• Condition: Infertility
• Association: INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients
• Population size: 353
• Population details: 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]), 72 age-matched healthy men
• Age: 17-56
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Congenital Hypogonadotropic Hypogonadism/Kallmann Syndrome, cryptorchidism

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients

Trabado S, Maione L, Bry-Gauillard H, Affres H, Salenave S, Sarfati J, Bouvattier C, Delemer B, Chanson P, Le Bouc Y, Brailly-Tabard S, Young J.

CONTEXT: Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. OBJECTIVE: To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. PATIENTS: We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. METHODS: Serum INSL3 was immunoassayed with a validated RIA. RESULTS: Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. CONCLUSIONS: INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH. FAU - Trabado, Séverine AU - Trabado S AD - Université de Paris-Sud (S.T., L.M., S.S., P.C., J.S., C.B., S.B.T., J.Y.), Faculté de Médecine Paris-Sud, Unité Mixte de Recherche-S693, Le Kremlin-Bicêtre, F-94276, France; Assistance Publique-Hôpitaux de Paris (S.T., S.B.T.), Hôpital de Bicêtre, Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin-Bicêtre, F-94275, France; Service d'Endocrinologie et des Maladies de la Reproduction (L.M., H.B.G., H.A., S.S., J.S., P.C., J.Y.), Département de Pédiatrie Endocrinienne (C.B.), Hôpital de Bicêtre, F-94275, France; Service d'Endocrinologie (B.D.), Centre Hospitalier Robert Debré, Reims F-51092, France; Inserm U693 (S.T., L.M., P.C., S.B.T., J.Y.), IFR93, Le Kremlin-Bicêtre, F94275, France; and Laboratoire d'Explorations Fonctionnelles Hôpital Trousseau (Y.L.B.), Assistance Publique-Hôpitaux de Paris and Université Pierre et Marie Curie and Inserm UMRS-938, Paris F-75012, France. FAU - Maione, Luigi AU - Maione L FAU - Bry-Gauillard, Hélène AU - Bry-Gauillard H FAU - Affres, Hélène AU - Affres H FAU - Salenave, Sylvie AU - Salenave S FAU - Sarfati, Julie AU - Sarfati J FAU - Bouvattier, Claire AU - Bouvattier C FAU - Delemer, Brigitte AU - Delemer B FAU - Chanson, Philippe AU - Chanson P FAU - Le Bouc, Yves AU - Le Bouc Y FAU - Brailly-Tabard, Sylvie AU - Brailly-Tabard S