title: Short-term energy deprivation alters activin a and follistatin but not inhibin B levels of lean healthy women in a leptin-independent manner.
abstract: BACKGROUND
  Leptin is a potent modulator of the hypothalamic-pituitary-gonadal axis mediating the effect of energy deprivation on several hypothalamic-pituitary-peripheral axes. Activin A, inhibin B, and follistatin (FST) also regulate the hypothalamic-pituitary-gonadal axis in humans. It remains unknown whether energy deprivation affects these hormone levels in a leptin-dependent or -independent manner.
  
  
  OBJECTIVE
  We investigated 1) day-night variability patterns of activin, inhibin, and FST in the fed state, 2) whether their levels are affected by fasting, and 3) whether such an effect is mediated by leptin in physiological replacement or pharmacological doses.
  
  
  METHODS
  We conducted two studies in healthy, eumenorrheic females, each comprising three separate admissions. In study 1, six women were maintained for 72 h 1) on isocaloric diet, 2) fasting while receiving placebo, or 3) fasting while receiving metreleptin in physiological replacement doses. In study 2, five women were administered physiological or pharmacological metreleptin doses (0.01, 0.1, or 0.3 mg/kg i.v. four times daily).
  
  
  RESULTS
  Neither activin A nor FST had a pulsatile or day-night variability pattern. Inhibin B levels were also nonpulsatile, but a trend toward a day-night pattern was noted. When compared with the fed state, inhibin B levels remained unchanged, whereas FST levels increased (P = 0.01) and activin A decreased (P = 0.01) in the fasting state. These changes were not corrected with metreleptin administered in replacement or pharmacological doses.
  
  
  CONCLUSIONS
  Short-term energy deprivation alters levels of activin A and FST, but these effects are not mediated by leptin.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02130, USA..
authors.forename: Vasiliki A
authors.initials: VA
authors.lastname: Moragianni
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Aronis
authors.forename: John P
authors.initials: JP
authors.lastname: Chamberland
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D028341:Activins / Q000097:blood*; D000328:Adult; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D038681:Follistatin / Q000097:blood*; D005508:Food Deprivation / Q000502:physiology*; D006801:Humans; D007265:Inhibins / Q000097:blood*; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D038681:Follistatin; D020738:Leptin; C422405:activin A; C422364:inhibin B; D028341:Activins; D007265:Inhibins