title: Differential sleep-wake sensitivity of gonadotropin-releasing hormone secretion to progesterone inhibition in early pubertal girls.
abstract: BACKGROUND
  Early pubertal luteinizing hormone (LH), and by inference gonadotropin-releasing hormone (GnRH), pulse secretion is marked by high nocturnal but low daytime frequency; however, the underlying mechanisms remain unclear. Plasma concentrations of progesterone, the major regulator of GnRH frequency in women, increase in the early morning in early pubertal girls and may help slow daytime GnRH frequency.
  
  
  OBJECTIVE
  To evaluate the effect of progesterone on LH pulse frequency in early to mid-pubertal girls.
  
  
  METHODS
  Controlled interventional study.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  Eighteen non-obese, non-hyperandrogenemic Tanner 1-3 girls.
  
  
  METHODS
  Twelve-hour (19:00-07:00 h) blood sampling with or without oral progesterone administration (25-50 mg at 16:00 and 20:00 h).
  
  
  METHODS
  LH pulse frequency.
  
  
  RESULTS
  Girls receiving progesterone (n = 5) exhibited lower 12-hour LH pulse frequency than controls (n = 13), but this difference was not statistically significant (average interpulse intervals 196.0 ± 61.9 and 160.4 ± 67.1 min, respectively; p = 0.2793). In contrast to controls, however, girls receiving progesterone exhibited no LH pulses during waking hours (19:00-23:00 h; estimated interpulse interval 326.0 ± 52.7 vs. 212.0 ± 120.9 min; p = 0.0376), while nighttime (23:00-07:00 h) interpulse intervals were similar (174.8 ± 62.0 vs. 167.5 ± 76.9 min, respectively; p = 0.7750).
  
  
  CONCLUSIONS
  Exogenous progesterone acutely suppressed daytime, but not nocturnal, LH pulse frequency in early to mid-pubertal girls, suggesting that GnRH pulse frequency is differentially regulated by progesterone depending on sleep status.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Jessicah S P
authors.initials: JS
authors.lastname: Collins
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCartney
mesh_terms: D000293:Adolescent; D002648:Child; D002940:Circadian Rhythm / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D011374:Progesterone / Q000378:metabolism*; D011627:Puberty / Q000378:metabolism; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone