title: Corticotropin-releasing hormone (CRH)-immunoreactive (IR) axon varicosities target a subset of growth hormone-releasing hormone (GHRH)-IR neurons in the human hypothalamus.
abstract: It is a general consensus that stress is one of the major factors that suppresses growth. Previous studies revealed that the catecholaminergic and neuropeptide Y (NPY) systems, involved in the activation of stress-related neuronal circuits, influence growth hormone (GH)-release via modulating growth hormone-releasing hormone (GHRH) secretion. Indeed, catecholaminergic and NPY-immunoreactive (IR) axon varicosities abut on the surface of the GHRH neurons forming contacts. These juxtapositions appear to be real synapses and may represent the morphological substrate of the impact of stress on growth. In addition to catecholamines and NPY, there is a vast amount of evidence that corticotropin-releasing hormone (CRH), a major stress hormone, also influences GH secretion. Whether this modulatory effect is direct, or indirect, via the hypothalamic GHRH system, has not been elucidated yet. In the present study, we examined the possibility that CRH influences GH secretion via modulating the GHRH release by direct synaptic mechanisms. Since the verification of these synapses by electron microscopy is problematic in human due to the long post mortem time, in order to reveal the putative CRH-GHRH juxtapositions, light microscopic double label immunohistochemistry was utilized. In the infundibular nucleus, a subset (6%) of the GHRH perikarya received abutting CRH fiber varicosities forming multiple contacts while passing by. No gaps appeared between the contacting elements. The morphology of these CRH-GHRH juxtapositions suggests that, among other neurotransmitters/neuromodulators, CRH influences growth by modulating the hypothalamic GHRH secretion via direct synaptic mechanisms.
authors.affiliation: Laboratory of Neuroendocrine Organization, Lake Erie College of Osteopathic Medicine, Erie, PA, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Peroski
authors.affiliation: Laboratory of Neuroendocrine Organization, Lake Erie College of Osteopathic Medicine, Erie, PA, United States.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Proudan
authors.affiliation: Laboratory of Neuroendocrine Organization, Lake Erie College of Osteopathic Medicine, Erie, PA, United States.
authors.forename: George
authors.initials: G
authors.lastname: Grignol
authors.affiliation: Department of Epidemiology & Public Health and Anatomy & Neurobiology, University of Maryland, School of Medicine, 10 S Pine Street, MSTF 977, Baltimore, MD, United States. Electronic address: imerchen@epi.umaryland.edu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Merchenthaler
authors.affiliation: Laboratory of Neuroendocrine Organization, Lake Erie College of Osteopathic Medicine, Erie, PA, United States.
authors.forename: Bertalan
authors.initials: B
authors.lastname: Dudas
mesh_terms: D000369:Aged, 80 and over; D001369:Axons / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*
chemical_list: D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone
keywords: CRH; GHRH; Growth; Growth hormone; Hypothalamus