title: Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration.
abstract: Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25-34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists.
authors.affiliation: INSERM U693, Université Paris-Sud, Faculté de Médecine Paris-Sud, Assistance Publique–Hôpitaux de Paris, Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sonigo
authors.forename: Justine
authors.initials: J
authors.lastname: Bouilly
authors.forename: Nadège
authors.initials: N
authors.lastname: Carré
authors.forename: Virginie
authors.initials: V
authors.lastname: Tolle
authors.forename: Alain
authors.initials: A
authors.lastname: Caraty
authors.forename: Javier
authors.initials: J
authors.lastname: Tello
authors.forename: Fabian-Jesus
authors.initials: FJ
authors.lastname: Simony-Conesa
authors.forename: Robert
authors.initials: R
authors.lastname: Millar
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D000818:Animals; D000858:Anovulation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D059648:Kisspeptins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D011388:Prolactin / Q000008:administration & dosage / Q000633:toxicity; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D006065:Gonadotropins, Pituitary; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin