title: Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty.
abstract: Some patients with idiopathic hypogonadotropic hypogonadism (IHH) undergo spontaneous activation of their hypothalamic-pituitary-gonadal axis resulting in normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal.
  
  
  
  To assess the responsiveness of the GnRH neuronal network to exogenous kisspeptin administration in IHH patients who have undergone reversal.
  
  
  
  Six men with congenital IHH and evidence for reversal.
  
  
  
  Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to iv boluses of kisspeptin (0.24-2.4 nmol/kg) and GnRH (75 ng/kg).
  
  
  
  Individuals with sustained reversal of their hypogonadotropism (spontaneous LH pulses) responded to exogenous kisspeptin with a GnRH-induced LH pulse. Individuals who had reversal but then subsequently suffered relapse of their IHH (loss of spontaneous LH pulsatility) did not respond to kisspeptin.
  
  
  
  The ability of kisspeptin to stimulate a GnRH-induced LH pulse correlates with the presence of endogenous LH pulses. These data suggest that reversal of hypogonadotropism, and by extension sexual maturation, may be due to the acquisition of kisspeptin responsiveness.
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Lippincott
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: Yee-Ming
authors.initials: YM
authors.lastname: Chan
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: Angela
authors.initials: A
authors.lastname: Delaney
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: Dianali
authors.initials: D
authors.lastname: Rivera-Morales
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (M.F.L., Y.-M.C., D.R.-M., S.B.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (Y.-M.C.), Department of Medicine, Boston Children's Hospital, and Division of Sleep Medicine (J.P.B.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Unit on Genetics of Puberty and Reproduction (A.D.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Seminara
mesh_terms: D000293:Adolescent; D000328:Adult; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D020249:Hormone Replacement Therapy; D006728:Hormones / Q000097:blood*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000378:metabolism* / Q000534:rehabilitation; D059648:Kisspeptins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011627:Puberty / Q000187:drug effects* / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D006728:Hormones; C106628:KISS1 protein, human; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone