title: Penile neuronal nitric oxide synthase and its regulatory proteins are present in hypothalamic and spinal cord regions involved in the control of penile erection.
abstract: Control of penile erection requires the coordination of the hypothalamus and the L6-S1 region of the spinal cord. Erection requires the activation of neuronal nitric oxide synthase (nNOS), which is tightly regulated. Because variants of nNOS (penile nNOS: PnNOS) and the N-methyl-D-aspartate receptor (truncated NMDAR subunit 1: NMDAR1-T) as well as protein inhibitor of NOS (PIN) have all been located in the pelvic ganglia and penile nerves, this work aims to determine whether these proteins are also present in the hypothalamus. It was found that PnNOS, the brain-type nNOS, and PIN, were expressed in the hypothalamus. In contrast, NMDAR1-T was expressed only in the penis, whereas the brain-type NMDAR1 was present in the brain and sacral spinal cord and not in the penis. PnNOS was found in the media preoptic area, posterior magnocellular, and the parvocellular regions of the paraventricular nucleus, supraoptic nucleus, septohypothalamic nucleus, medial septum, cortex, and in some of the nNOS staining neurons throughout the brain. It was absent in the organum vasculosum of the lamina terminalis. PIN staining was present in neurons of the medial preoptic area, paraventricular nucleus, medial septum, and cortex, but not in the supraoptic nucleus, septohypothalamic nucleus, or organum vasculosum of the lamina terminalis. Colocalization between PnNOS and PIN was found in the medial preoptic area, medial septum, and cortex, and less in the paraventricular nucleus. PnNOS and oxytocin were colocalized in the paraventricular nucleus and supraoptic nucleus. In hypothalamic extracts, recombinant PIN-GST protein bound to PnNOS in the extracts and partially inhibited NOS activity. These results indicate that both nNOS variants, and their respective regulatory proteins are present and colocalize in the hypothalamic and spinal cord regions involved in penile erection.
authors.affiliation: Research and Education Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Magee
authors.forename: Dolores
authors.initials: D
authors.lastname: Vernet
authors.forename: Jacob
authors.initials: J
authors.lastname: Rajfer
authors.forename: Nestor F
authors.initials: NF
authors.lastname: González-Cadavid
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis*; D029721:Drosophila Proteins; D004398:Dyneins; D004791:Enzyme Inhibitors / Q000032:analysis; D007031:Hypothalamus / Q000737:chemistry* / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052248:Nitric Oxide Synthase Type I; D010410:Penile Erection; D010413:Penis / Q000294:innervation*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis*; D013116:Spinal Cord / Q000737:chemistry* / Q000201:enzymology
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; C409466:NR1 NMDA receptor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D004398:Dyneins