title: Involvement of neurokinin receptors in the control of pulsatile luteinizing hormone secretion in rats.
abstract: It has recently been shown that neurokinin B, a tachykinin, is associated with GnRH pulse generation in sheep and goats. The aim of the present study was to clarify the role of tachykinin receptors in the control of LH secretion in rats. To this end, we evaluated the effect of CS-003, an antagonist for all three neurokinin receptors (NK1, NK2 and NK3 receptors), on pulsatile LH secretion in both sexes of rats with different routes of administration. Both oral and third ventricular administration of CS-003 suppressed LH secretion in both sexes of gonadectomized animals. Furthermore, intact male rats with oral administration of CS-003 showed decreased serum testosterone levels, which might be due to suppressed LH secretion. None of the three subtype-specific neurokinin receptor antagonists showed a significant effect on LH secretion in ovariectomized rats when each antagonist was singly administered. The present results suggest that neurokinins play a role in the control of pulsatile GnRH/LH secretion via multiple neurokinin receptors in both male and female rats.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co. Ltd., Shizuoka, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Noritake
authors.forename: Toshiki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ohsawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimomura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbuissho
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
mesh_terms: D000818:Animals; D003499:Cyclic S-Oxides / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D015287:Neurokinin B / Q000378:metabolism* / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: C530698:1-(2-(2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl)ethyl)spiro(benzo(c)thiophene-1(3H),4'-piperidine)-2-oxide; D003499:Cyclic S-Oxides; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D013739:Testosterone; D015287:Neurokinin B; D007986:Luteinizing Hormone