title: Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.
abstract: Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination.
authors.affiliation: Inserm U693, université Paris-Sud, 94275 Le Kremlin-Bicêtre, France; Laboratoire d'hormonologie et génétique, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Trabado
authors.affiliation: Service d'endocrinologie et des maladies de la reproduction, Hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lamothe
authors.affiliation: Service d'endocrinologie et des maladies de la reproduction, Hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Luigi
authors.initials: L
authors.lastname: Maione
authors.affiliation: Département d'endocrinologie pédiatrique, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvattier
authors.affiliation: Service d'endocrinologie et des maladies de la reproduction, Hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Sarfati
authors.affiliation: Inserm U693, université Paris-Sud, 94275 Le Kremlin-Bicêtre, France; Laboratoire d'hormonologie et génétique, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.affiliation: Inserm U693, université Paris-Sud, 94275 Le Kremlin-Bicêtre, France; Service d'endocrinologie et des maladies de la reproduction, Hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France. Electronic address: jacques.young@bct.aphp.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
mesh_terms: D003456:Cryptorchidism / Q000209:etiology; D004359:Drug Therapy, Combination; D005640:Follicle Stimulating Hormone / Q000172:deficiency / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007006:Hypogonadism / Q000503:physiopathology*; D007231:Infant, Newborn; D007265:Inhibins / Q000378:metabolism; D017436:Kallmann Syndrome / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000172:deficiency / Q000627:therapeutic use; D008297:Male; D010413:Penis / Q000002:abnormalities; D011627:Puberty / Q000502:physiology; D011974:Receptors, LH / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013737:Testis / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D006728:Hormones; D011974:Receptors, LH; D011994:Recombinant Proteins; C422364:inhibin B; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: AMH; Estradiol; Hypogonadism; Hypogonadisme; INSL3; Inhibin B; Inhibine B; Kallmann; Testosterone; Testostérone