Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region

• Published in: PloS one 2013-08, Vol.8 (8), p.e72369-e72369
• Main Authors: Hrabovszky, Erik, Borsay, Beáta Á, Rácz, Kálmán, Herczeg, László, Ciofi, Philippe, Bloom, Stephen R, Ghatei, Mohammad A, Dhillo, Waljit S, Liposits, Zsolt
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Arcuate nucleus; Arcuate Nucleus of Hypothalamus - cytology; Arcuate Nucleus of Hypothalamus - metabolism; Autocrine signalling; Autopsies; Autopsy; Axons; Axons - metabolism; Capillaries; Capillaries - metabolism; Cell Body - metabolism; Endocrinology; Experiments; Female; Females; Fluorescent Antibody Technique; Gene expression; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - metabolism; Gonadotropins; Humans; Hypothalamus; Immunoreactivity; Kiss1 protein; Kisspeptins - analysis; Kisspeptins - metabolism; Laboratory animals; Male; Males; Middle Aged; Neurobiology; Neurohormones; Neurokinin; Neurokinin B; Neurokinin B - analysis; Neurokinin B - metabolism; Neurons; Neuropeptides; Neurophysiology; Neurosciences; Neurosecretion; Nuclei; Paracrine signalling; Pituitary (anterior); Pituitary Gland - blood supply; Pituitary Gland - metabolism; Pituitary hormones; Post-menopause; Postmenopausal women; Protein Transport; Pulse generators; Regulators; Rodents; Studies; Substance P; Substance P - analysis; Substance P - metabolism; Tachykinin; Tachykinin receptors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0072369

Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.