title: Neurokinin-3 receptor activation in the retrochiasmatic area is essential for the full pre-ovulatory luteinising hormone surge in ewes.
abstract: Neurokinin B (NKB) is essential for human reproduction and has been shown to stimulate luteinising hormone (LH) secretion in several species, including sheep. Ewes express the neurokinin-3 receptor (NK3R) in the retrochiasmatic area (RCh) and there is one report that placement of senktide, an NK3R agonist, therein stimulates LH secretion that resembles an LH surge in ewes. In the present study, we first confirmed that local administration of senktide to the RCh produced a surge-like increase in LH secretion, and then tested the effects of this agonist in two other areas implicated in the control of LH secretion and where NK3R is found in high abundance: the preoptic area (POA) and arcuate nucleus (ARC). Bilateral microimplants containing senktide induced a dramatic surge-like increase in LH when given in the POA similar to that seen with RCh treatment. By contrast, senktide treatment in the ARC resulted in a much smaller but significant increase in LH concentrations suggestive of an effect on tonic secretion. The possible role of POA and RCh NK3R activation in the LH surge was next tested by treating ewes with SB222200, an NK3R antagonist, in each area during an oestradiol-induced LH surge. SB222200 in the RCh, but not in the POA, reduced the LH surge amplitude by approximately 40% compared to controls, indicating that NK3R activation in the former region is essential for full expression of the pre-ovulatory LH surge. Based on these data, we propose that the actions of NKB in the RCh are an important component of the pre-ovulatory LH surge in ewes.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Porter
authors.forename: S M
authors.initials: SM
authors.lastname: Hileman
authors.forename: S L
authors.initials: SL
authors.lastname: Hardy
authors.forename: C C
authors.initials: CC
authors.lastname: Nestor
authors.forename: M N
authors.initials: MN
authors.lastname: Lehman
authors.forename: R L
authors.initials: RL
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012756:Sheep; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C109112:SB 222200; C054724:senktide; D013373:Substance P; D007986:Luteinizing Hormone
keywords: GnRH; LH surge; NK3R; neurokinins; oestrogen