title: Differential modulation of gonadotropin responses to kisspeptin by aminoacidergic, peptidergic, and nitric oxide neurotransmission.
abstract: Kisspeptins (Kp), products of the Kiss1 gene, have emerged as essential elements in the control of GnRH neurons and gonadotropic secretion. However, despite considerable progress in the field, to date limited attention has been paid to elucidate the potential interactions of Kp with other neurotransmitters known to centrally regulate the gonadotropic axis. We characterize herein the impact of manipulations of key aminoacidergic (glutamate and GABA), peptidergic (NKB, Dyn, and MCH), and gaseous [nitric oxide (NO)] neurotransmission on gonadotropin responses to Kp-10 in male rats. Blockade of ionotropic glutamate receptors (of the NMDA and non-NMDA type) variably decreased LH responses to Kp-10, whereas activation of both ionotropic and metabotropic receptors, which enhanced LH and FSH release per se, failed to further increase gonadotropin responses to Kp-10. In fact, coactivation of metabotropic receptors attenuated LH and FSH responses to Kp-10. Selective activation of GABA(A) receptors decreased Kp-induced gonadotropin secretion, whereas their blockade elicited robust LH and FSH bursts and protracted responses to Kp-10 when combined with GABA(B) receptor inhibition. Blockade of Dyn signaling (at κ-opioid receptors) enhanced LH responses to Kp-10, whereas activation of Dyn and NKB signaling modestly reduced Kp-induced LH and FSH release. Finally, MCH decreased basal LH secretion and modestly reduced FSH responses to Kp-10, whereas LH responses to Kp-10 were protracted after inhibition of NO synthesis. In summary, we present herein evidence for the putative roles of glutamate, GABA, Dyn, NKB, MCH, and NO in modulating gonadotropic responses to Kp in male rats. Our pharmacological data will help to characterize the central interactions and putative hierarchy of key neuroendocrine pathways involved in the control of the gonadotropic axis.
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Cordoba, Spain.
authors.forename: David
authors.initials: D
authors.lastname: García-Galiano
authors.forename: Rafael
authors.initials: R
authors.lastname: Pineda
authors.forename: Juan
authors.initials: J
authors.lastname: Roa
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Pino
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sánchez-Garrido
authors.forename: Juan M
authors.initials: JM
authors.lastname: Castellano
authors.forename: Enrique
authors.initials: E
authors.lastname: Aguilar
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Navarro
authors.forename: Leonor
authors.initials: L
authors.lastname: Pinilla
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
mesh_terms: D000818:Animals; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D059648:Kisspeptins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015287:Neurokinin B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D010907:Pituitary Hormones / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D007028:Hypothalamic Hormones; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D008543:Melanins; D010907:Pituitary Hormones; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone; D015287:Neurokinin B; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004398:Dyneins