title: Role of neurokinin B in the control of female puberty and its modulation by metabolic status.
abstract: Human genetic studies have revealed that neurokinin B (NKB) and its receptor, neurokinin-3 receptor (NK3R), are essential elements for normal reproduction; however, the precise role of NKB-NK3R signaling in the initiation of puberty remains unknown. We investigated here the regulation of Tac2 and Tacr3 mRNAs (encoding NKB and NK3R, respectively) in female rats and demonstrated that their hypothalamic expression is increased along postnatal maturation. At puberty, both genes were widely expressed throughout the brain, including the lateral hypothalamic area and the arcuate nucleus (ARC)/medial basal hypothalamus, where the expression of Tacr3 increased across pubertal transition. We showed that central administration of senktide (NK3R agonist) induced luteinizing hormone (LH) secretion in prepubertal and peripubertal females. Conversely, chronic infusion of an NK3R antagonist during puberty moderately delayed the timing of vaginal opening (VO) and tended to decrease LH levels. The expression of NKB and its receptor was sensitive to changes in metabolic status during puberty, as reflected by a reduction in Tacr3 (and, to a lesser extent, Tac2) expression in the ARC after a 48 h fast. Yet, acute LH responses to senktide in pubertal females were preserved, if not augmented, under fasting conditions, suggesting sensitization of the NKB-NK3R-gonadotropin-releasing hormone signaling pathway under metabolic distress. Moreover, repeated administration of senktide to female rats with pubertal arrest due to chronic undernutrition rescued VO (in ∼50% of animals) and potently elicited LH release. Altogether, our observations suggest that NKB-NK3R signaling plays a role in pubertal maturation and that its alterations may contribute to pubertal disorders linked to metabolic stress and negative energy balance.
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Spain. nalovic@gmail.com
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Navarro
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Pino
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sánchez-Garrido
authors.forename: David
authors.initials: D
authors.lastname: García-Galiano
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Hobbs
authors.forename: María
authors.initials: M
authors.lastname: Manfredi-Lozano
authors.forename: Silvia
authors.initials: S
authors.lastname: León
authors.forename: Susana
authors.initials: S
authors.lastname: Sangiao-Alvarellos
authors.forename: Juan M
authors.initials: JM
authors.lastname: Castellano
authors.forename: Donald K
authors.initials: DK
authors.lastname: Clifton
authors.forename: Leonor
authors.initials: L
authors.lastname: Pinilla
authors.forename: Robert A
authors.initials: RA
authors.lastname: Steiner
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D055442:Metabolome / Q000502:physiology*; D015287:Neurokinin B / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000378:metabolism / Q000502:physiology; D012741:Sexual Maturation / Q000502:physiology*
chemical_list: D018042:Receptors, Neurokinin-3; D015287:Neurokinin B