Topography and Associations of Leu-Enkephalin and Luteinizing Hormone-Releasing Hormone Neuronal Systems in the Human Diencephalon

Abstract

Although several studies indicated that leu-enkephalin controls gonadal function, the morphological substrate of this modulation is unknown. To reveal potential interaction sites between leu-enkephalin and LH-releasing hormone (LHRH) in the hypothalamus, the distribution and connections of leu-enkephalin-immunoreactive (IR) and LHRH-IR systems were examined in the human diencephalon using double-label immunohistochemistry. First the leu-enkephalin-IR and LHRH-IR neural elements were mapped, then the maps of the two different neurotransmitter systems were superimposed unveiling the overlapping areas. The putative juxtapositions between leu-enkephalin-IR and LHRH-IR structures were revealed with double label immunocytochemistry. Close contacts were detected in the medial preoptic area and in the infundibulum/median eminence. In these areas, diaminobenzidine-silver-intensified, black leu-enkephalin-IR fibers abutted fusiform, brown, diaminobenzidine-labeled LHRH neurons often forming multiple contacts. Examination of semithin sections of these close associations with the aid of oil immersion revealed no cleft between the contacting LHRH-IR and leu-enkephalin-IR elements. Our findings indicate that the juxtapositions between LHRH-IR and leu enkephalin-IR neurons may be functional synapses forming the morphological substrate of the leu-enkephalin-modulated LHRH secretion in the human diencephalon. Moreover, the wide distribution of leu-enkephalin-IR elements suggests leu-enkephalin control of other diencephalic functions as well.

Afferent Neuronal Control of Type-I Gonadotropin Releasing Hormone Neurons in the Human

“…These experiments established that Leu-enkephalin-IR cell bodies are concentrated in three different regions: (i) in the periventricular area of the tuberal region, (ii) in the infundibulum in the close proximity of the portal vessels, and (iii) in the medial preoptic area periventricularly (180). Leu-enkephalin-IR fibers established appositions to GnRH-IR cell bodies and dendrites mainly in the infundibulum and the median eminence (180). …”

“…The β-endorphin-IR input to human GnRH neurons is likely to arise from local sources given that the mediobasal hypothalamus contained a high number of β-endorphin-IR perikarya (178). Interestingly, while a series of immunohistochemical studies showed that GnRH neurons in front of the lamina terminalis do not receive significant input from axons containing catecholamines (179), NPY (15), SP (50), leu-enkephalin (180), and CRH (147), β-endorphin containing axons did innervate this rostral subpopulation of GnRH neurons (178). …”

“…Direct regulatory actions of central enkephalinergic pathways on human GnRH neurons have been addressed with dual-label immunohistochemical studies (180). These experiments established that Leu-enkephalin-IR cell bodies are concentrated in three different regions: (i) in the periventricular area of the tuberal region, (ii) in the infundibulum in the close proximity of the portal vessels, and (iii) in the medial preoptic area periventricularly (180).…”

Three‐Dimensional Representation of the Neurotransmitter Systems of the Human Hypothalamus: Inputs of the Gonadotrophin Hormone‐Releasing Hormone Neuronal System

“…1). Although there are plenty of publications reporting the distribution of leu‐enkephalin in the rodent brain (70–73), only one study has reported the distribution of leu‐enkephalin in the human hypothalamus (74). In the human hypothalamus, the majority of leu‐enkephalin‐IR perikarya are present in the periventricular area of the hypothalamus and the infundibulum.…”

Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human

“…Most peptide neurotransmitters identified within neuronal afferents to human GnRH neurons are synthesized in distinct cell populations of the medial hypothalamus (Hrabovszky and Liposits, 2013 ) and include neuropeptide Y (Dudás et al, 2000 ), substance P (Dudás and Merchenthaler, 2002a ; Hrabovszky et al, 2013 ), galanin (Dudás and Merchenthaler, 2004a ), corticotropin-releasing hormone (Dudás and Merchenthaler, 2002b ), kisspeptin (Hrabovszky et al, 2010 , 2011 , 2012b ; Molnár et al, 2012 ), neurokinin B (Hrabovszky et al, 2011 , 2012b ; Molnár et al, 2012 ), endorphins (Dudás and Merchenthaler, 2004b ), enkephalins (Dudás and Merchenthaler, 2003 ), dynorphins (Dahl et al, 2009 ), RF-amide related peptide/gonadotropin-inhibiting hormone (Ubuka et al, 2009 ) and cocaine- and amphetamine-regulated transcript (Skrapits et al, 2014 ).…”