Summary
The neuropeptide thyrotropin releasing hormone (TRH) is capable of influencing both neuronal mechanisms in the brain and the activity of the pituitary-thyroid endocrine axis. By the use of immunocytochemical techniques, first the ultrastructural features of TRH-immunoreactive (IR) perikarya and neuronal processes were studied, and then the relationship between TRH-IR neuronal elements and dopamine-β-hydroxylase (DBH) or phenylethanolamine-N-methyltransferase (PNMT)-IR catecholaminergic axons was analyzed in the parvocellular subnuclei of the hypothalamic paraventricular nucleus (PVN). In control animals, only TRH-IR axons were detected and some of them seemed to follow the contour of immunonegative neurons. Colchicine treatment resulted in the appearance of TRH-IR material in parvocellular neurons of the PVN. At the ultrastructural level, immunolabel was associated with rough endoplasmic reticulum, free ribosomes and neurosecretory granules. Non-labelled axons formed synaptic specializations with both dendrites and perikarya of the TRH-synthesizing neurons. TRH-IR axons located in the parvo-cellular units of the PVN exhibited numerous intensely labelled dense-core and fewer small electron lucent vesicles. These axons were frequently observed to terminate on parvocellular neurons, forming both bouton- and en passant-type connections. The simultaneous light microscopic localization of DBH or PNMT-IR axons and TRH-synthesizing neurons demonstrated that catecholaminergic fibers established contacts with the dendrites and cell bodies of TRH-IR neurons. Ultrastructural analysis revealed the formation of asymmetric axo-somatic and axo-dendritic synaptic specializations between PNMT-immunopositive, adrenergic axons and TRH-IR neurons in the periventricular and medial parvocellular subnuclei of the PVN.
These morphological data indicate that the hypophysiotrophic, thyrotropin releasing hormone synthesizing neurons of the PVN are directly influenced by the central epinephrine system and that TRH may act as a neurotransmitter or neuromodulator upon other paraventricular neurons.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aizawa T, Greer MA (1981) Delineation of the hypothalamic area controlling thyrotropin secretion in the rat. Endocrinology 109:1731–1738
Beauvillain JC, Tramu G, Mazzuca M (1987) Fine structural studies of growth-hormone-releasing factor (GRF)-immunoreactive neurons and their synaptic connections in the guinea pig arcuate nucleus. J Comp Neurol 255:110–123
Berod A, Hartman BK, Pujol JF (1981) Importance of fixation in immunohistochemistry: use of formaldehyde solutions at variable pH for the localization of tyrosine hydroxylase. J Histochem Cytochem 29:884–850
Brownstein MJ, Palkovits M, Saavedra JM, Bassiri RM, Utiger RD (1974) Thyrotropin-releasing hormone in specific nuclei of rat brain. Science 185:267–269
Burgus R, Dunn TF, Desiderio D, Guillemin R (1969) Structure moleculaire du facteur hypothalamique hypophysiotrope TRF d'origine ovine: mise evidence par spectrometrie de masse de la sequence. CR Acad Sci, Ser D 269:1870–1893
Chen YF, Ramirez VD (1981) Serotonin stimulates thyrotropin-releasing hormone release from superfused rat hypothalami. Endocrinology 108:2359–2366
Dieguez C, Foord SM, Peters JR, Hall R, Scanlon MF (1984) Interactions among epinephrine, thyrotropin (TSH)-releasing hormone, dopamine, and somatostatin in the control of TSH secretion in vitro. Endocrinology 114:957–961
Gallyas F (1982) Suppression of argyrophil III reaction by mercapto-compounds. A prerequisite for intensification of histochemical reactions by physical developers. Acta Histochem 70:99–105
Greer MA (1957) Studies on the influence of the central nervous system on anterior pituitary function. In: Pincus G (ed) Recent progress in hormone research. Academic Press, New York, pp 67–104
Grimm Y, Reichlin S (1973) Thyrotropin-releasing hormone (TRH): neurotransmitter regulation of secretion by mouse hypothalamic tissue in vitro. Endocrinology 93:626–631
Hirooka Y, Hollander CS, Suzuki S, Ferdinand P, Juan S-I (1978) Somatostatin inhibits release of thyrotropin releasing factor from organ cultures of rat hypothalamus. Proc Natl Acad Sci USA 75:4509–4513
Hisano S, Ishizuka H, Nishiyama T, Tsuruo Y, Katoh S, Daikoku S (1986) Immunoelectron microscopic observations of hypothalamic TRH-containing neurons in rats. Exp Brain Res 63:495–504
Hökfelt T, Fuxe K, Johansson O, Jeffcoate S, White N, (1975a) Distribution of thyrotropin-releasing hormone (TRH) in the central nervous system as revealed with immunohistochemistry. Eur J Pharmacol 34:389–392
Hökfelt T, Fuxe K, Johansson O, Jeffcoate S, White N (1975b) Thyrotropin releasing hormone (TRH)-containing nerve terminals in certain brain stem nuclei and in the spinal cord. Neurosci Lett 1:133–139
Ishikawa K, Inoue K, Tosaka H, Shimada O, Suzuki M (1984) Immunohistochemical characterization of thyrotropin-releasing hormone-containing neurons in rat septum. Neuroendocrinology 39:448–452
Jackson IMD, Reichlin S (1974) Thyrotropin-releasing hormone (TRH): Distribution in hypothalamic and extrahypothalamic brain tissues of mammalian and submammalian chordates. Endocrinology 95:854–862
Jackson IMD, Reichlin S (1979) Distribution and biosynthesis of TRH in the nervous system. In: Collu R, Barbeau A, Ducharme JR, Rochefort JG (eds) Central nervous system effects of hypothalamic hormones and other peptides. Raven Press, New York, pp 3–54
Jackson IMD, Lechan RM (1987) Thyrotropin releasing hormone. In: Martin J, Brownstein M, Krieger D (eds) Brain peptides update, vol 1. John Wiley & Sons, New York, pp 101–125
Jackson IMD, Wu P, Lechan RM (1985) Immunohistochemical localization in the rat brain of the precursor for thyrotropin-releasing hormone. Science 229:1097–1099
Jeffcoate SL, Fraser HM, Gunn A, White N (1973) Radioimmunoassay of thyrotrophin releasing hormone. J Endocrinol 59:191–192
Johansson O, Hökfelt T, Jeffcoate SL, White N, Sternberger LA (1980) Ultrastructural localization of TRH-like immunoreactivity. Exp Brain Res 38:1–10
Joseph-Bravo P, Charli JL, Palacios JM, Kordon C (1979) Effect of neurotransmitters on the in vitro release of immunoreactive thyrotropin-releasing hormone from rat mediobasal hypothalamus. Endocrinology 104:801–806
King JC, Anthony ELP (1983) Biosynthesis of LHRH: inferences from immunocytochemical studies. Peptides 4:963–970
Klibanski A, Milbury PE, Chin WW, Ridgway EC (1983) Direct adrenergic stimulation of the release of thyrotropin and its subunits from the thyrotrope in vitro. Endocrinology 113:1244–1249
Krisch B (1980) Two types of luliberin-immunoreactive perikarya in the preoptic area of the rat. Cell Tissue Res 212:443–455
Krulich L (1982) Neurotransmitter control of thyrotropin secretion. Neuroendocrinology 35:139–147
Lechan RM, Jackson IMD (1982) Immunohistochemical localization of thyrotropin-releasing hormone in the rat hypothalamus and pituitary. Endocrinology 111:55–65
Lechan RM, Molitch ME, Jackson IMD (1983) Distribution of immunoreactive human growth hormone-like material and thyrotropin-releasing hormone in the rat central nervous system: Evidence for their coexistence in the same neurons. Endocrinology 112:877–884
Lechan RM, Snapper SB, Jacobson S, Jackson IMD (1984) The distribution of thyrotropin-releasing hormone (TRH) in the Rhesus monkey spinal cord. Peptides 5 (Suppl):185–194
Lechan RM, Wu P, Jackson IMD, Wolf H, Cooperman S, Mandel G, Goodman RH (1986a) Thyrotropin-releasing hormone precursor: characterization in rat brain. Science 231:159–161
Lechan RM, Wu P, Jackson IMD (1986b) Immunolocalization of the thyrotropin-releasing hormone prohormone in the rat central nervous system. Endocrinology 119:1210–1216
Liposits Zs, Görcs T, Török A, Domány S, Sétáló G (1983a) Simultaneous localiation of two different tissue antigens based on the silver intensified PAP-DAB and on the traditional PAP-DAB method. Acta Morphol Hung 31:365–369
Liposits Zs, Görcs T, Sétáló G, Lengvári I, Flerkó B, Vigh S, Schally AV (1983b) Ultrastructural characteristics of immunolabelled, corticotropin releasing factor (CRF)-synthesizing neurons in the rat brain. Cell Tissue Res 229:191–196
Liposits Zs, Lengvári I, Vigh S, Schally AV, Flerkó B (1983c) Immunohistological detection of degenerating CRF-immunoreactive nerve fibers in the median eminence after lesion of paraventricular nucleus of the rat. A light and electron microscopic study. Peptides 4:941–953
Liposits Zs, Sétáló G, Flerkó B (1984) Application of the silver-gold intensified 3,3′-diaminobenzidine chromogen to the light and electron microscopic detection of the LH-RH system of the rat brain. Neuroscience 13:513–524
Liposits Zs, Phelix C, Paull WK (1986a) Adrenergic innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. Histochemistry 84:201–205
Liposits Zs, Sherman D, Phelix C, Paull WK (1986b) A combined light and electron microscopic immunocytochemical method for the simultaneous localization of multiple tissue antigens. Histochemistry 85:95–106
Liposits Zs, Sievers L, Paull WK, Lechan RM, Coen CW, Culler MD, Merchenthaler I, Jackson IMD (1987a) Monoamine and peptidergic innervation of chemically characterized hypophysiotrophic neurons. Abst of sec world congr of neurosci, Budapest, 1987. Neuroscience 22 (Suppl):810
Liposits Zs, Lechan RM, Paull WK, Wu P, Jackson IMD (1987b) Adrenergic innervation of thyrotropin releasing hormone (TRH) synthesizing neurons of the rat hypothalamus. Soc Neurosci Abst 17 (in press)
Maeda K, Frohman LA (1980) Release of somatostatin and thyrotropin-releasing hormone from rat hypothalamic fragments in vitro. Endocrinology 106:1837–1842
Martin JB, Reichlin S (1972) Plasma thyrotropin (TRH) response to hypothalamic electrical stimulation and to injection of synthetic thyrotropin releasing hormone (TRH). Endocrinology 90:1079–1085
Montoya E, Wilber JF, Lorincz M (1979) Catecholaminergic control of thyrotropin secretion. J Lab Clin Med 93:887–94
Nishiyama T, Kawano H, Tsuruo Y, Maegawa M, Hisano S, Adachi T, Daikoku S, Suzuki M (1985) Hypothalamic thyrotropin-releasing hormone (TRH)-containing neurons involved in the hypothalamic-hypophysial-thyroid axis. Light microscopic immunohistochemistry. Brain Res 345:205–218
Reichlin S (1986) Neuroendocrine control of thyrotropin secretion. In: Ingbar SH, Braverman LE (eds) Werner's the thyroid. JB Lippincott, Philadelphia, pp 241–266
Schaeffer JM, Axelrod J, Brownstein MJ (1977) Regional differences in dopamine-mediated release of TRH-like material from synaptosomes. Brain Res 138:571–574
Schally AV, Redding TW, Bowers CY, Barrett JF (1969) Isolation and properties of porcine thyrotropin-releasing hormone. J Biol Chem 244:4077–4088
Shioda S, Nakai Y, Sato A, Sunayama S, Shimoda Y (1986) Electron-microscopic cytochemistry of the catecholaminergic innervation of TRH neurons in the rat hypothalamus. Cell Tissue Res 245:247–252
Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabelled antibody enzyme method of immunochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antiperoxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333
Streit P, Reubi JC (1977) A new and sensitive staining method for axonally transported peroxidase (HRP) in the pigeon visual system. Brain Res 126:530–537
Terry LC (1986) Regulation of thyrotropin secretion by the central epinephrine system. Neuroendocrinology 42:102–108
van den Pol AN (1982) The magnocellular and parvocellular paraventricular nucleus of rat: Intrinsic organization. J Comp Neurol 206:317–345
Winokur A, Utiger RD (1974) Thyrotropin-releasing hormone: Regional distribution in rat brain. Science 185:265–267
Wu P, Lechan RM, Jackson IMD (1987) Identification and characterization of thyrotropin-releasing hormone precursor peptides in rat brain. Endocrinology 121:108–115
Zamboni L, DeMartino L (1967) Buffered picric acid-formaldehyde: a new rapid fixative for electron microscopy. J Cell Biol 35:148A
Author information
Authors and Affiliations
Additional information
Supported by NIH research grants NS19266 and DK34540
Rights and permissions
About this article
Cite this article
Liposits, Z., Paull, W.K., Wu, P. et al. Hypophysiotrophic thyrotropin releasing hormone (TRH) synthesizing neurons. Histochemistry 88, 1–10 (1987). https://doi.org/10.1007/BF00490159
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00490159