title: Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex steroid feedback.
abstract: OBJECTIVE
  Does sex-steroid feedback influence gonadotrophin responses to kisspeptin-10?
  
  
  CONCLUSIONS
  Gonadotrophin response to kisspeptin-10 is enhanced in sex-steroid deficient post-menopausal women and suppressed in women taking pharmacological doses of exogenous estrogen and progestogen.
  
  
  BACKGROUND
  Kisspeptin, a novel hypothalamic neuropeptide, stimulates gonadotrophin secretion by stimulating GnRH secretion and has been shown in animal models to play a pivotal role in mediating sex steroid feedback. As estrogen feedback occurs at both the hypothalamus and the pituitary levels, we hypothesized that the stimulatory effect of kisspeptin-10 in women would be dependent on prevailing sex steroid milieu.
  
  
  METHODS
  An experimental study of a novel neuropeptide in women-10 in the early follicular phase, 6 post-menopausal and 8 taking sex-steroid contraceptives (combined pill, n = 4; progestogen implants, n = 4) with suppressed LH secretion. Gonadotrophin secretion was followed for 60 min after kisspeptin administration.
  
  
  METHODS
  The gonadotrophin response to intravenous kisspeptin-10 (0.3 µg/kg) in women in the early follicular phase was compared with that in the presence of low endogenous sex steroids/high gonadotrophin secretion (post-menopausal women) and in women taking sex-steroid contraceptives (combined pill, n = 4; progestogen implants, n = 4) with suppressed LH secretion. Area under the curve (AUC) of gonadotrophin secretion sampled at 15 min intervals over 60 min before and after kisspeptin-10 was analysed.
  
  
  RESULTS
  Kisspeptin-10 stimulated LH secretion in follicular (ΔAUC 2.3 ± 0.8 IU/l h, P = 0.009), post-menopausal (5.3 ± 0.9 IU/l h P 0.002) and progestogen (2.6 ± 0.8 IU/l h P 0.05) groups but not in women taking combined pill (0.9 ± 0.4 IU/l h P 0.13). FSH secretion was significantly increased only in post-menopausal women (ΔAUC 2.6 ± 0.8 IU/l h P = 0.03) with changes of <0.5 IU/l h observed in the other three groups. Both LH and FSH responses in post-menopausal women were significantly larger than the other groups (one-way ANOVA analysis of ΔAUC; LH (P = 0.012) and FSH (P = 0.001)].
  
  
  CONCLUSIONS
  This study only assessed acute responses to an intravenous bolus of kisspeptin-10 administration, and the impact of continuous exposure to kisspeptin-10 on LH pulse frequency in women remains to be studied to fully understand the translational potential.
  
  
  CONCLUSIONS
  Gonadotrophin secretion in women is stimulated by kisspeptin-10. These results suggest that the pituitary gonadotrope is a functionally important locus of estrogen feedback in women and also inform potential translational applications of kisspeptin in reproductive endocrine disorders.
  
  
  BACKGROUND
  Medical Research Council (UK).
  None.
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, EH16 4TJ Edinburgh, UK. j.george@ed.ac.uk
authors.forename: J T
authors.initials: JT
authors.lastname: George
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
authors.forename: R P
authors.initials: RP
authors.lastname: Millar
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D059648:Kisspeptins / Q000494:pharmacology*; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000494:pharmacology*
chemical_list: D003276:Contraceptives, Oral; D006062:Gonadotropins; C106628:KISS1 protein, human; D059648:Kisspeptins; D011374:Progesterone; D004958:Estradiol