title: Continuous Kisspeptin Administration in Postmenopausal Women: Impact of Estradiol on Luteinizing Hormone Secretion.
abstract: Kisspeptin stimulates the reproductive endocrine cascade in both men and women. Circulating sex steroids are thought to modulate the ability of kisspeptin to stimulate gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release.
  
  
  
  To probe the effects of sex steroids on kisspeptin-stimulated GnRH-induced LH pulses.
  
  
  
  Eight healthy postmenopausal women.
  
  
  
  Subjects underwent every-10-minute blood sampling to measure GnRH-induced LH secretion at baseline and in response to a continuous kisspeptin infusion (12.5 µg/kg/h) over 24 hours. A subset of the participants also received kisspeptin (0.313 µg/kg) and GnRH (75 ng/kg) intravenous boluses.
  
  
  
  Postmenopausal women are resistant to the stimulatory effect of continuous kisspeptin on LH secretion. Postmenopausal women receiving estradiol replacement therapy are also resistant to kisspeptin initially, but they demonstrate a significant increase in LH pulse amplitude in direct proportion to the circulating estradiol concentration and duration of kisspeptin administration.
  
  
  
  Kisspeptin administration has complex effects on GnRH, and by extension, on LH secretion. The ability of kisspeptin to affect LH secretion can be modulated by the ambient sex-steroid milieu in a time- and dose-dependent manner.
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Lippincott
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.|Division of Endocrinology, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Yee-Ming
authors.initials: YM
authors.lastname: Chan
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Dianali
authors.initials: D
authors.lastname: Rivera Morales
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Seminara
mesh_terms: D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D059648:Kisspeptins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D004967:Estrogens; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone