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Ann Endocrinol (Paris). 2017 Oct;78 Suppl 1:S31-S40. doi: 10.1016/S0003-4266(17)30923-X.

Contrôle de l’axe gonadotrope : nouveaux aspects physiologiques et thérapeutiques: Control of the gonadotrope axis: new physiologic and therapeutic aspects.

[Article in French]

Author information

1
Université Paris-Sud, Orsay 91400, France; Service d'endocrinologie et des maladies de la reproduction, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France; Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France. Electronic address: luigi.maione@aphp.fr.
2
Service d'endocrinologie, hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 75012 Paris, France; Université Pierre-et-Marie-Curie, 75006, Paris, France.
3
Université Paris-Sud, Orsay 91400, France; Service d'endocrinologie et des maladies de la reproduction, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France; INSERM UMR-1185, faculté de médecine Paris-Sud, 94276 Le Kremlin-Bicêtre, France.

Abstract

The endocrine and exocrine functions of the gonads are controlled by the gonadotrope axis, whose master regulator is the hypothalamic decapeptide GnRH. The Kisspeptin/Neurokinin B (Kp/NkB) neuronendocrine system is the main physiologic regulator of GnRH neurons. The Kp/NkB system is currently considered the key mediator for the hypothalamic negative feedback exerted by sex steroids and prolactin, as well as by various metabolic signals. Intrinsic alterations or regulatory abnormalities of Kp/NkB system lead to various gonadotrope axis puberty and fertility dysfunctions. Molecular inactivations of Kp/NkB system actors are associated with some forms of congenital hypogonadotropic hypogonadism without anosmia. The Kp/NkB System is also involved in a few forms of precocious puberty. Finally, the Kp/NKB system is also implicated in gonadotrope axis alterations leading to functional hypothalamic amenorrhea or hyperprolactinemia. NkB is particularly and directly involved in vasomotor menopausal hot flushes mechanism. Various Kp/NkB agonist/antagonist compounds have been developed during the last ten years, and are currently being evaluated in humans. These molecules have potential applications not only in rare genetic diseases with Kp/NkB alterations, but also in various gonadotrope axis-related diseases or in vitro fertilization. The administration of NkB antagonists in menopausal women represents a real therapeutic advance because of their impressive effect in controlling vasomotor menopausal hot flushes.

KEYWORDS:

Bouffées de chaleur de la ménopause; Congenital hypogonadotropic hypogonadism; GnRH; Hypogonadisme hypogonadotrophique congénital; Kisspeptin; Kisspeptine; Neurokinin B; Neurokinine B; Post-menopausal hot flushes; climatére

PMID:
29157487
DOI:
10.1016/S0003-4266(17)30923-X
[Indexed for MEDLINE]

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