title: Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human.
abstract: Hypophysiotropic projections of gonadotropin-releasing hormone (GnRH)-synthesizing neurons form the final common output way of the hypothalamus in the neuroendocrine control of reproduction. Several peptidergic neuronal systems of the medial hypothalamus innervate human GnRH cells and mediate crucially important hormonal and metabolic signals to the reproductive axis, whereas much less is known about the contribution of the lateral hypothalamic area to the afferent control of human GnRH neurons. Orexin (ORX)- and melanin-concentrating hormone (MCH)-synthesizing neurons of this region have been implicated in diverse behavioral and autonomic processes, including sleep and wakefulness, feeding and other functions. In the present immunohistochemical study, we addressed the anatomical connectivity of these neurons to human GnRH cells in post-mortem hypothalamic samples obtained from autopsies. We found that 38.9 ± 10.3% and 17.7 ± 3.3% of GnRH-immunoreactive (IR) perikarya in the infundibular nucleus of human male subjects received ORX-IR and MCH-IR contacts, respectively. On average, each 1 mm segment of GnRH dendrites received 7.3 ± 1.1 ORX-IR and 3.7 ± 0.5 MCH-IR axo-dendritic appositions. Overall, the axo-dendritic contacts dominated over the axo-somatic contacts and represented 80.5 ± 6.4% of ORX-IR and 76.7 ± 4.6% of MCH-IR inputs to GnRH cells. Based on functional evidence from studies of laboratory animals, the direct axo-somatic and axo-dendritic input from ORX and MCH neurons to the human GnRH neuronal system may convey critical metabolic and other homeostatic signals to the reproducive axis. In this study, we also report the generation and characterization of new antibodies for immunohistochemical detection of GnRH neurons in histological sections.
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Skrapits
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Vivien
authors.initials: V
authors.lastname: Kanti
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Savanyú
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Maurnyi
authors.affiliation: Department and Clinic for Production Animals, Faculty of Veterinary Science, Szent István University Üllő, Hungary ; MTA-SZIE Large Animal Clinical Research Group, Dóra major Üllő, Hungary.
authors.forename: Ottó
authors.initials: O
authors.lastname: Szenci
authors.affiliation: Department and Clinic for Production Animals, Faculty of Veterinary Science, Szent István University Üllő, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Horváth
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine of the University of Debrecen Debrecen, Hungary.
authors.forename: Beáta Á
authors.initials: BÁ
authors.lastname: Borsay
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine of the University of Debrecen Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Herczeg
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary ; Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors.forename: Erik
authors.initials: E
authors.lastname: Hrabovszky
keywords: human; hypothalamus; immunohistochemistry; melanin-concentrating hormone; orexin