title: Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.
abstract: The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling with respect to controlling puberty onset. The present study aimed to determine the role of endogenous NKB-NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion and the timing of puberty onset, and also whether precocious pubertal onset as a result of an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with i.c.v. cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus (as markers of puberty) compared to controls in both normal and high-fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and that the LH pulse amplitude was reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and the associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat.
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, School of Medicine, King's College London, Guy's Campus, London, UK; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Li
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: M H
authors.initials: MH
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Shao
authors.forename: L
authors.initials: L
authors.lastname: Poston
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.forename: K T
authors.initials: KT
authors.lastname: O'Byrne
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood* / Q000187:drug effects; D008297:Male; D008845:Microinjections; D015287:Neurokinin B / Q000502:physiology*; D011627:Puberty / Q000187:drug effects* / Q000502:physiology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D011804:Quinolines; D018042:Receptors, Neurokinin-3; C109112:SB 222200; D015287:Neurokinin B; D007986:Luteinizing Hormone
keywords: LH pulse frequency; neurokinin B; over-nutrition; puberty; rat