title: Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?
abstract: There is now general agreement that neurokinin B (NKB) acts via neurokinin-3-receptor (NK3R) to stimulate secretion of GnRH and LH in several species, including rats, mice, sheep, and humans. However, the roles of two other tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and NK2R, respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this study, we examined the possible role of these tachykinins in control of the reproductive axis in sheep. Immunohistochemistry was used to describe the expression of SP and NK1R in the ovine diencephalon and determine whether these proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more widespread. However, there was very low coexpression of SP or NK1R in kisspeptin cells and none in GnRH neurons. We next determined the minimal effective dose of these three tachykinins that would stimulate LH secretion when administered into the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated LH secretion. Moreover, the relative potency of these three neuropeptides parallels the relative selectivity of NK3R. Based on these anatomical and pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway for the control of GnRH secretion by tachykinins in ewes.
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Fergani
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Leanne
authors.initials: L
authors.lastname: Mazzella
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Lique M
authors.initials: LM
authors.lastname: Coolen
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Richard B
authors.initials: RB
authors.lastname: McCosh
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Hardy
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Nora
authors.initials: N
authors.lastname: Newcomb
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Pasha
authors.initials: P
authors.lastname: Grachev
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Lehman
authors.affiliation: Departments of Neurobiology and Anatomical Sciences (C.F., M.N.L.) and Physiology (L.M.C., N.N.), University of Mississippi Medical Center, Jackson, Mississippi 39216-4505; and Department of Physiology and Pharmacology (L.M., R.B.M., S.L.H., P.G., R.L.G.), West Virginia University Health Sciences Center, Morgantown, West Virginia 26506-9229.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goodman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D059648:Kisspeptins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D015288:Neurokinin A / Q000008:administration & dosage; D015287:Neurokinin B / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D059648:Kisspeptins; D018040:Receptors, Neurokinin-1; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D015288:Neurokinin A; D015287:Neurokinin B; D007986:Luteinizing Hormone