{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:56:08Z","timestamp":1778730968109,"version":"3.51.4"},"reference-count":39,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>The objective of this study was to determine the effect of deep sleep fragmentation on LH secretion in pubertal children.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Setting:<\/jats:title>\n                  <jats:p>Studies were performed in a clinical research center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects:<\/jats:title>\n                  <jats:p>Fourteen healthy pubertal children (11.3\u201314.1 y) participated in the study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions:<\/jats:title>\n                  <jats:p>Subjects were randomized to two overnight studies with polysomnography and frequent blood sampling, with or without deep sleep disruption via auditory stimuli.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>An average of 68.1 \u00b110.7 (\u00b1 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 \u00b1 0.2 min vs normal 7.1 \u00b1 0.8 min, P &amp;lt; .001), and increasing the number of transitions between non-rapid eye movement (NREM), REM, and wake (disrupted 274.5 \u00b1 33.4 vs normal 131.2 \u00b1 8.1, P = .001). There were no differences in mean LH (normal: 3.2 \u00b1 0.4 vs disrupted: 3.2 \u00b1 0.5 IU\/L), LH pulse frequency (0.6 \u00b1 0.06 vs 0.6 \u00b1 0.07 pulses\/h), or LH pulse amplitude (2.8 \u00b1 0.4 vs 2.8 \u00b1 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 &amp;lt; .001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2014-3563","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T19:09:45Z","timestamp":1418152185000},"page":"1062-1070","source":"Crossref","is-referenced-by-count":21,"title":["Accumulated Deep Sleep Is a Powerful Predictor of LH Pulse Onset in Pubertal Children"],"prefix":"10.1210","volume":"100","author":[{"given":"N. D.","family":"Shaw","sequence":"first","affiliation":[{"name":"Reproductive Endocrine Unit (N.D.S., T.K., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114"},{"name":"Division of Endocrinology (N.D.S.), Boston, Massachusetts 02115"},{"name":"Children\u2019s Hospital Boston, Division of Sleep Medicine (N.D.S., J.E.H.), Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. P.","family":"Butler","sequence":"additional","affiliation":[{"name":"Harvard Medical School, and Division of Sleep and Circadian Disorders (J.P.B.), Brigham and Women\u2019s Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Nemati","sequence":"additional","affiliation":[{"name":"Harvard School of Engineering and Applied Sciences (S.N.), Harvard University, Cambridge, Massachusetts 02138"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kangarloo","sequence":"additional","affiliation":[{"name":"Reproductive Endocrine Unit (N.D.S., T.K., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Ghassemi","sequence":"additional","affiliation":[{"name":"Electrical Engineering and Computer Science, Massachusetts Institute of Technology (M.G.), Cambridge, Massachusetts 02142"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine (A.M.), University of California, San Diego, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Reproductive Endocrine Unit (N.D.S., T.K., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114"},{"name":"Children\u2019s Hospital Boston, Division of Sleep Medicine (N.D.S., J.E.H.), Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"issue":"12","key":"2020071618511814300_B1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1056\/NEJM197209212871203","article-title":"Synchronization of augmented luteinizing hormone secretion with sleep during puberty","volume":"287","author":"Boyar","year":"1972","journal-title":"N Engl J Med"},{"issue":"11","key":"2020071618511814300_B2","doi-asserted-by":"crossref","first-page":"E2055","DOI":"10.1210\/jc.2012-2692","article-title":"Insights into puberty: the relationship between sleep stages and pulsatile LH secretion","volume":"97","author":"Shaw","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2020071618511814300_B3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.5664\/jcsm.2928","article-title":"Obstructive sleep apnea (OSA) in preadolescent girls is associated with delayed breast development compared to girls without OSA","volume":"9","author":"Shaw","year":"2013","journal-title":"J Clin Sleep Med"},{"issue":"235","key":"2020071618511814300_B4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in pattern of pubertal changes in girls","volume":"44","author":"Marshall","year":"1969","journal-title":"Arch Dis Child"},{"issue":"1","key":"2020071618511814300_B5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/sleep\/27.1.110","article-title":"Method for detection of respiratory cycle-related EEG changes in sleep-disordered breathing","volume":"27","author":"Chervin","year":"2004","journal-title":"Sleep"},{"key":"2020071618511814300_B6","volume-title":"The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology, and Technical Specifications","author":"Iber","year":"2007"},{"issue":"3","key":"2020071618511814300_B7","first-page":"858","article-title":"The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency","volume":"79","author":"Adams","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2020071618511814300_B8","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1073\/pnas.0706446105","article-title":"Slow-wave sleep and the risk of type 2 diabetes in humans","volume":"105","author":"Tasali","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2020071618511814300_B9","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.steroids.2012.10.010","article-title":"Dynamics of serum testosterone during the menstrual cycle evaluated by daily measurements with an ID-LC-MS\/MS method and a 2nd generation automated immunoassay","volume":"78","author":"Bui","year":"2013","journal-title":"Steroids"},{"issue":"1\u20132","key":"2020071618511814300_B10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cca.2007.10.020","article-title":"Mass spectrometric and physiological validation of a sensitive, automated, direct immunoassay for serum estradiol using the Architect","volume":"388","author":"Sluss","year":"2008","journal-title":"Clin Chim Acta"},{"issue":"3","key":"2020071618511814300_B11","first-page":"1028","article-title":"Free \u03b1-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies","volume":"84","author":"Hayes","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2020071618511814300_B12","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1172\/JCI107454","article-title":"Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms","volume":"52","author":"Santen","year":"1973","journal-title":"J Clin Invest"},{"issue":"5","key":"2020071618511814300_B13","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nn1228","article-title":"Multiple neural spike train data analysis: state-of-the-art and future challenges","volume":"7","author":"Brown","year":"2004","journal-title":"Nat Neurosci"},{"issue":"6","key":"2020071618511814300_B14","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1210\/endo-127-6-2884","article-title":"Maturation of the hypothalamic control of pulsatile gonadotropin-releasing hormone secretion at onset of puberty: II. Reduced potency of an inhibitory autofeedback","volume":"127","author":"Bourguignon","year":"1990","journal-title":"Endocrinology"},{"issue":"5","key":"2020071618511814300_B15","first-page":"1794","article-title":"Decrease in gonadotropin-releasing hormone (GnRH) pulse frequency with aging in postmenopausal women","volume":"85","author":"Hall","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2020071618511814300_B16","doi-asserted-by":"crossref","first-page":"e1001110","DOI":"10.1371\/journal.pcbi.1001110","article-title":"A Granger causality measure for point process models of ensemble neural spiking activity","volume":"7","author":"Kim","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"2020071618511814300_B17","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ccm.2010.02.002","article-title":"Pediatric obstructive sleep apnea syndrome","volume":"31","author":"Katz","year":"2010","journal-title":"Clin Chest Med"},{"issue":"6","key":"2020071618511814300_B18","doi-asserted-by":"crossref","first-page":"e11356","DOI":"10.1371\/journal.pone.0011356","article-title":"Obstructive sleep apnea alters sleep stage transition dynamics","volume":"5","author":"Bianchi","year":"2010","journal-title":"PLoS One"},{"issue":"2","key":"2020071618511814300_B19","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1210\/endo.132.2.8425489","article-title":"Hormone ontogeny in the ovine fetus. XXVII. Pulsatile and copulsatile secretion of luteinizing hormone, follicle-stimulating hormone, growth hormone, and prolactin in late gestation: a new method for the analysis of copulsatility","volume":"132","author":"Albers","year":"1993","journal-title":"Endocrinology"},{"issue":"3","key":"2020071618511814300_B20","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1210\/jcem-73-3-569","article-title":"Analysis of the copulsatility of anterior pituitary hormones","volume":"73","author":"Veldhuis","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"issue":"5246","key":"2020071618511814300_B21","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1126\/science.271.5246.216","article-title":"Activation of ventrolateral preoptic neurons during sleep","volume":"271","author":"Sherin","year":"1996","journal-title":"Science"},{"issue":"4","key":"2020071618511814300_B22","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cell.2005.09.027","article-title":"Feedback loops link odor and pheromone signaling with reproduction","volume":"123","author":"Boehm","year":"2005","journal-title":"Cell"},{"issue":"7","key":"2020071618511814300_B23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-2826.2011.02145.x","article-title":"Depolarising and hyperpolarising actions of GABA(A) receptor activation on gonadotrophin-releasing hormone neurones: towards an emerging consensus","volume":"23","author":"Herbison","year":"2011","journal-title":"J Neuroendocrinol"},{"issue":"1","key":"2020071618511814300_B24","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0306-4522(02)00308-1","article-title":"Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species","volume":"115","author":"Gaus","year":"2002","journal-title":"Neuroscience"},{"issue":"Pt 10","key":"2020071618511814300_B25","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/brain\/awu222","article-title":"Sleep is related to neuron numbers in the ventrolateral preoptic\/intermediate nucleus in older adults with and without Alzheimer\u2019s disease","volume":"137","author":"Lim","year":"2014","journal-title":"Brain"},{"issue":"4","key":"2020071618511814300_B26","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/cne.903390408","article-title":"Topography of neurons expressing luteinizing hormone-releasing hormone gene transcripts in the human hypothalamus and basal forebrain","volume":"339","author":"Rance","year":"1994","journal-title":"J Comp Neurol"},{"issue":"20","key":"2020071618511814300_B27","doi-asserted-by":"crossref","first-page":"6896","DOI":"10.1523\/JNEUROSCI.5344-13.2014","article-title":"Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep\/wake regulation","volume":"34","author":"Tsunematsu","year":"2014","journal-title":"J Neurosci"},{"issue":"40","key":"2020071618511814300_B28","doi-asserted-by":"crossref","first-page":"17217","DOI":"10.1073\/pnas.0908200106","article-title":"Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction","volume":"106","author":"Wu","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"8","key":"2020071618511814300_B29","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1210\/en.2010-0022","article-title":"Minireview: kisspeptin\/neurokinin B\/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion","volume":"151","author":"Lehman","year":"2010","journal-title":"Endocrinology"},{"issue":"48","key":"2020071618511814300_B30","doi-asserted-by":"crossref","first-page":"19846","DOI":"10.1073\/pnas.1211517109","article-title":"Role for kisspeptin\/neurokinin B\/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature","volume":"109","author":"Mittelman-Smith","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2020071618511814300_B31","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1210\/jc.2008-1655","article-title":"Blunted sleep-related luteinizing hormone rise in healthy premenarcheal pubertal girls with elevated body mass index","volume":"94","author":"Bordini","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2020071618511814300_B32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1210\/jc.2008-1252","article-title":"Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls","volume":"94","author":"McCartney","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"5 Pt 1","key":"2020071618511814300_B33","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1164\/ajrccm.159.5.9809079","article-title":"Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems","volume":"159","author":"Redline","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"issue":"2 Pt 1","key":"2020071618511814300_B34","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1164\/ajrccm.162.2.9908058","article-title":"Sleep architecture and respiratory disturbances in children with obstructive sleep apnea","volume":"162","author":"Goh","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"2020071618511814300_B35","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.jpeds.2006.08.067","article-title":"Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy","volume":"149","author":"Tauman","year":"2006","journal-title":"J Pediatr"},{"issue":"5","key":"2020071618511814300_B36","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1183\/09031936.00106710","article-title":"Adenotonsillectomy improves slow-wave activity in children with obstructive sleep apnoea","volume":"37","author":"Ben-Israel","year":"2011","journal-title":"Eur Respir J"},{"issue":"8 Pt 1","key":"2020071618511814300_B37","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1164\/ajrccm.164.8.2008146","article-title":"Effect of continuous positive airway pressure on sleep architecture in the sleep apnea-hypopnea syndrome: a randomized controlled trial","volume":"164","author":"McArdle","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"2020071618511814300_B38","doi-asserted-by":"crossref","first-page":"e921","DOI":"10.1542\/peds.2014-1696","article-title":"Insufficient sleep in adolescents and young adults: an update on causes and consequences","volume":"134","author":"Owens","year":"2014","journal-title":"Pediatrics"},{"key":"2020071618511814300_B39","doi-asserted-by":"crossref","first-page":"S164","DOI":"10.1542\/peds.2007-2329C","article-title":"Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report","volume":"120","author":"Barlow","year":"2007","journal-title":"Pediatrics"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/3\/1062\/10434851\/jcem1062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/100\/3\/1062\/10434851\/jcem1062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T04:06:53Z","timestamp":1594958813000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/100\/3\/1062\/2839725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,1]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2014-3563","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,1]]}}}