title: Accumulated deep sleep is a powerful predictor of LH pulse onset in pubertal children.
abstract: BACKGROUND
  During puberty, reactivation of the reproductive axis occurs during sleep, with LH pulses specifically tied to deep sleep. This association suggests that deep sleep may stimulate LH secretion, but there have been no interventional studies to determine the characteristics of deep sleep required for LH pulse initiation.
  
  
  OBJECTIVE
  The objective of this study was to determine the effect of deep sleep fragmentation on LH secretion in pubertal children.
  
  
  METHODS
  Studies were performed in a clinical research center.
  
  
  METHODS
  Fourteen healthy pubertal children (11.3-14.1 y) participated in the study.
  
  
  METHODS
  Subjects were randomized to two overnight studies with polysomnography and frequent blood sampling, with or without deep sleep disruption via auditory stimuli.
  
  
  RESULTS
  An average of 68.1 ±10.7 (± SE) auditory stimuli were delivered to interrupt deep sleep during the disruption night, limiting deep sleep to only brief episodes (average length disrupted 1.3 ± 0.2 min vs normal 7.1 ± 0.8 min, P < .001), and increasing the number of transitions between non-rapid eye movement (NREM), REM, and wake (disrupted 274.5 ± 33.4 vs normal 131.2 ± 8.1, P = .001). There were no differences in mean LH (normal: 3.2 ± 0.4 vs disrupted: 3.2 ± 0.5 IU/L), LH pulse frequency (0.6 ± 0.06 vs 0.6 ± 0.07 pulses/h), or LH pulse amplitude (2.8 ± 0.4 vs 2.8 ± 0.4 IU/L) between the two nights. Poisson process modeling demonstrated that the accumulation of deep sleep in the 20 minutes before an LH pulse, whether consolidated or fragmented, was a significant predictor of LH pulse onset (P < .001).
  
  
  CONCLUSIONS
  In pubertal children, nocturnal LH augmentation and pulse patterning are resistant to deep sleep fragmentation. These data suggest that, even when fragmented, deep sleep is strongly related to activation of the GnRH pulse generator.
authors.affiliation: Reproductive Endocrine Unit (N.D.S., T.K., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (N.D.S.), Children's Hospital Boston, Division of Sleep Medicine (N.D.S., J.E.H.), Harvard Medical School, and Division of Sleep and Circadian Disorders (J.P.B.), Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115; Harvard School of Engineering and Applied Sciences (S.N.), Harvard University, Cambridge, Massachusetts 02138; Electrical Engineering and Computer Science, Massachusetts Institute of Technology (M.G.), Cambridge, Massachusetts 02142; and Division of Pulmonary and Critical Care Medicine (A.M.), University of California, San Diego, La Jolla, California 92037.
authors.forename: N D
authors.initials: ND
authors.lastname: Shaw
authors.forename: J P
authors.initials: JP
authors.lastname: Butler
authors.forename: S
authors.initials: S
authors.lastname: Nemati
authors.forename: T
authors.initials: T
authors.lastname: Kangarloo
authors.forename: M
authors.initials: M
authors.lastname: Ghassemi
authors.forename: A
authors.initials: A
authors.lastname: Malhotra
authors.forename: J E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D017286:Polysomnography; D011379:Prognosis; D011627:Puberty / Q000097:blood / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000097:blood / Q000175:diagnosis; D012895:Sleep, REM
chemical_list: D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone