Skip to main content
Log in

Neurons of the rat hypothalamus reactive with antisera against endorphins, ACTH, MSH and β-LPH

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

In rat brains intraventricularly injected with colchicine, the same discrete neurons of the arcuate and ventromedial nuclei can be stained with antisera against α- and β-endorphins, (1-24)ACTH, (17-39)ACTH, α- and β-MSH, and β-LPH, as demonstrated by comparative studies in consecutive serial sections. These neurons are strongly reactive with anti-(17-39)ACTH, anti-β-endorphin, anti-α-MSH and anti-β-MSH, and more faintly stained with anti-α-endorphin, anti-β-LPH and anti-(1-24)ACTH. Exceptionally, neurons reactive with anti-(17-39)ACTH and anti-β-endorphin are poorly stained or completely negative with anti-α-MSH and anti-β-MSH. Immunoreactive fibers end in the lateral median eminence and in the arcuate nucleus proper, or form ascending pathways along the third ventricle. Comparative studies with other antisera or with the Falck and Hillarp technique show that these neurons differ from the elements producing LH-RH, somatostatin, neurophysin, oxytocin, vasopressin and dopamine.

These results suggest that the same neurons of the rat hypothalamus synthesize several neuropeptides identical with or immunologically related to endorphins, ACTH, α-MSH and β-LPH, probably arising from a common precursor molecule similar to that found in the corticotropic cells of the pituitary. These neuropeptides of a common cellular and molecular origin might be involved in basic processes of the central nervous system as neurotransmitters or neuromodulators.

Résumé

Dans les cerveaux de rats ayant reçu une injection intra-ventriculaire de colchicine, une même population de neurones du noyau arqué et du noyau ventro-médian est indifféremment immunoréactive à divers I.S. dirigés contre les endorphines (α et β), l'ACTH(1-24), l'ACTH(17-39), les MSH (α et β) et la β-LPH, comme le démontrent des études comparatives sur coupes sériées. Ces neurones sont intensément marqués par l'anti-ACTH(17-39), l'anti-β-endorphine, l'anti-α-MSH et l'anti-β-MSH et plus faiblement immunoréactifs à l'anti-α-endorphine, l'anti-β-LPH et l'anti-ACTH(1-24). Exceptionnellement, certains neurones immunoréactifs avec l'anti-ACTH(17-39) et l'anti-β-endorphine sont faiblement ou non reconnus par l'anti-α-MSH et l'anti-β-MSH. Les fibres immunoréactives se terminent dans l'éminence médiane latérale et dans le noyau arqué lui-même, ou forment des voies ascendantes le long du III∘ Ventricule. Des études comparatives avec d'autres I.S. ou avec la technique de Falck et Hillarp, montrent que ces neurones sont différents de ceux producteurs de LH-RH, de somatostatine, de neurophysine, d'ocytocine, de vasopressine et de dopamine.

Ces résultats suggèrent que certains neurones de l'hypothalamus du rat synthétisent plusieurs neuropeptides identiques aux ou immunologiquement très voisins des peptides du groupe endorphine, ACTH, α-MSH et β-LPH, vraisemblablement à partir d'un précurseur commun similaire à celui des cellules corticotropes adénohypophysaires. Ces neuropeptides ayant une origine cellulaire et moléculaire commune pourraient être impliqués comme neurotransmetteurs ou neuromodulateurs dans le fonctionnement du système nerveux central.

This work was supported by grants from the D.G.R.S.T. (contract n∘ 78.7.2749) and from the I.N.S.E.R.M. (contract n∘ 81.79.113)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

β-LPH:

β-lipotropin

ACTH:

corticotropin

MSH:

melanotropin

LH-RH:

luteinizing hormone-releasing hormone

CLIP:

corticotropin-like intermediate peptide

PAP:

peroxidase-anti-peroxidase

I.S.:

immune sera

References

  • Akil, H., Richardson, D.E., Barchas, T.D., Li, C.H.: Appearance of β-endorphin like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation. Proc. Natl. Acad. Sci. 75, 5170–5172 (1978)

    Google Scholar 

  • Barry, J., Dubois, M.P., Poulain, P.: LRF-producing cells of the mammalian hypothalamus: a fluorescent antibody study. Z. Zellforsch., 146, 351–366 (1973)

    Google Scholar 

  • Bertagna, X., Girard, F.: Données récentes sur le groupe des hormones hypophysaires mélanotropes et lipotropes (MSH-LPH) et sur les peptides cérébraux morphinomimétiques (endorphines). Ann. Endocrinol., 39, 201–213 (1978)

    Google Scholar 

  • Bloch, B., Bugnon, C., Lenys, D., Fellmann, D.: Description des neurones immunoréactifs à un immunsérum anti-β-endorphine, présents dans le noyau infundibulaire chez l'homme. C.R. Acad. Sci. 287 (D) (Paris), 309–312 (1978a)

    Google Scholar 

  • Bloch, B., Bugnon, C., Fellman, D., Lenys, D.: Immunocytochemical evidence that the same neurons in the human infundibular nucleus are stained with anti-endorphins and antisera of other related peptides. Neurosci. Lett., 10, 147–152 (1978b)

    Google Scholar 

  • Bloch, B., Bugnon, C., Fellmann, D., Lenys, D.: Présence de déterminants antigéniques de la β-LPH, de la β-MSH, de l'α-endorphine, de l'ACTH et de l'α-MSH dans les neurones révélés par l'anti-β-endorphine au niveau du noyau infundibulaire de l'homme. C.R. Acad. Sci., 287 (D) (Paris), 1019–1022 (1978c)

    Google Scholar 

  • Bloom, F., Segal, D., Ling, N., Guillemin, R.: Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness. Science, 194, 630–632 (1976)

    Google Scholar 

  • Bloom, F., Battenberg, E., Rossier, J., Guillemin, R.: Neurons containing β-endorphin in rat brain exist separately from those containing enkephalin: immunocytochemical studies. Proc. Natl. Acad. Sci., 75, 1591–1595 (1978)

    Google Scholar 

  • Bugnon, C., Bloch, B., Lenys, D., Fellmann, D.: Etude cyto-immunologique chez le foetus humain et chez l'homme adulte de neurones hypothalamiques susceptibles d'élaborer divers peptides de type MSH, ACTH, LPH et endorphines à partir d'un précurseur commun. J. Physiol. (Paris), 75, 67–87 (1979a)

    Google Scholar 

  • Bugnon, C., Bloch, B., Lenys, D., Fellmann, D.: Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins ACTH, MSH and β-LPH. Cell Tissue Res., 199, 177–196 (1979b)

    Google Scholar 

  • Bugnon, C., Bloch, B., Lenys, D., Gouget, A., Fellmann, D.: Comparative study of the neuronal populations containing β-endorphin, corticotropin and dopamine in the arcuate nucleus of the rat hypothalamus. Neurosci. Lett. (1979c), 14, 43–48 (1979c)

    Google Scholar 

  • Crine, P., Benjannet, S., Seidah, N.G., Lis, M., Chretien, M.: In vitro biosynthesis of β-endorphin in pituitary gland. Proc. Natl. Acad. Sci., 74, 1403–1406 (1977)

    Google Scholar 

  • De Wied, D.: Behavioral effects of neuropeptides related to ACTH, MSH and β-LPH. In: ACTH and related peptides: structure, regulation and action (D.T. Krieger and W.T. Ganong, eds.). Ann. N.Y. Acad. Sci., 297, 263–274 (1977)

  • Dupont, A., Cusan, L., Labrie, F., Coy, D.H., Li, C.H.: Stimulation of prolactin release in the rat by intraventricular injection of β-endorphin and methionine-enkephalin. Biochem. Biophys. Res. Commun., 75, 76–82 (1977)

    Google Scholar 

  • Fellmann, D.: Contribution à l'étude du système peptidergique hypothalamique à somatostatine. Etude cyto-immunologique comparative chez le foetus humain, le rat et le renard. Thèse Médecine. In: Ann. Sci. Université Besançon (section Médecine), n∘7, 1–156 (1978)

  • Follénius, E., Dubois, M.P.: Localisation immunocytologique de peptides analogues à l'α-endorphine dans certains neurones du noyau latéral du tuber de “Carassius auratus L.” et “Cyprinus carpio L.” C.R. Acad. Sci., (D) (Paris), 285, 1065–1068 (1977)

    Google Scholar 

  • Girod, G.: Apport de l'immunohistochimie à l'étude cytologique de l'adénohypophyse. Bull. Assoc. Anat. (Nancy), 62, 417–603 (1977)

    Google Scholar 

  • Guillemin, R., Ling, N., Vargo, T.: Radioimmunoassays for α-endorphin and β-endorphin. Biochem. Biophys. Res. Commun., 77, 361–366 (1977)

    Google Scholar 

  • Hosobuchi, Y., Rossier, J., Bloom, F.E., Guillemin, R.: Stimulation of human periaqueductal gray for pain relief increases immunoreactive β-endorphin in ventricular fluid. Science, 203, 279–181 (1979)

    Google Scholar 

  • Jacobowitz, D.M., O'Donohue, T.L.: α-melanocyte stimulating hormone: immunohistochemical identification and mapping in neurons of rat brain. Proc. Natl. Acad. Sci. 75, 6300–6304 (1978)

    Google Scholar 

  • Jaquet, Y.F.: Opiate effects after adrenocorticotropin or β-endorphin injection in the periaqueductal gray matter of rats. Science, 201, 1032–1034 (1978)

    Google Scholar 

  • Krieger, D.T., Liotta, A., Brownstein, M.J.: Presence of corticotropin in brain of normal and hypophysectomized rats. Proc. Natl. Acad. Sci., 74, 648–652 (1977a)

    Google Scholar 

  • Krieger, D.T., Liotta, A., Suda, T., Palkovits, M., Brownstein, M.J.: Presence of immunoassayable β-lipotropin in bovine brain and spinal cord: lack of concordance with ACTH concentrations. Biochem. Biophys. Res. Commun., 76, 930–936 (1977b)

    Google Scholar 

  • Larsson, L.I.: Corticotropin-like peptides in central nerves and in endocrine cells of gut and pancreas. Lancet, 2, 1321–1323 (1977)

    Google Scholar 

  • Lazarus, L.H., Ling, L., Guillemin, R.: β-Lipotropin as a prohormone for the morphinomimetic peptides endorphins and enkephalins. Proc. Natl. Acad. Sci., 73, 2156–2159 (1976)

    Google Scholar 

  • Liotta, A.S., Suda, T., Krieger, D.T.: β-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant β-endorphin. Proc. Natl. Acad. Sci., 75, 2950–2954 (1978)

    Google Scholar 

  • Liotta, A.S., Gildersleeve, D., Brownstein, M.J., Krieger, D.T.: Biosynthesis in vitro of immunoreactive 31,000-dalton corticotropin/β-endorphin-like material by bovine hypothalamus. Proc. Natl. Acad. Sci., 76, 1448–1452 (1979)

    Google Scholar 

  • Lowry, P.J., Silman, R.E., Hope, J.: Structure and biosynthesis of peptides related to corticotropins and β-melanotropins. In: ACTH and related peptides: structure, regulation and action (D.T. Krieger and W.F. Ganong, eds.). Ann. N.Y. Acad. Sci., 297, 49–62 (1977)

  • Mains, R.E., Eipper, B.A., Ling, N.: Common precursor to corticotropins and endorphins. Proc. Natl. Acad. Sci., 74, 3014–3018 (1977)

    Google Scholar 

  • Matsukura, S., Yoshimi, H., Sueoka, S., Kataoka, K., Ono, T., Ohgushi, N.: The regional distribution of immunoreactive β-endorphin in the monkey brain. Brain Res., 159, 228–233 (1978)

    Google Scholar 

  • Meglio, M., Hosobuchi, Y., Loh, H.H., Adams, J.E., Li, C.H.: β-Endorphin: behavioral and analgesic activity in cats. Proc. Natl. Acad. Sci., 74, 774–776 (1977)

    Google Scholar 

  • Meites, J., Bruni, J.F., Van Vugt, A., Smith, A.F.: Relation of endogenous opioid peptides and morphine to neuroendocrine functions. Life Sci., 24, 1325–1336 (1979)

    Google Scholar 

  • Moldow, R., Yalow, R.S.: Extrahypophysial distribution of corticotropin as a function of brain size. Proc. Natl. Acad. Sci., 75, 994–998 (1978)

    Google Scholar 

  • Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A.C.Y., Cohen, S.N., Numa, S.: Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor. Nature, 278, 423–427 (1979)

    Google Scholar 

  • Nilaver, G., Zimmerman, E.A., Defendini, R., Liotta, A.S., Krieger, D.T., Brownstein, M.J.: Adrenocorticotropin and β-lipotropin in the hypothalamus: localization in the same arcuate neurons by sequential immunocytochemical procedure. J. Cell Biol., 81, 50–58 (1979)

    Google Scholar 

  • Oliver, C., Porter, J.C.: Distribution and characterization of α-melanocyte stimulating hormone in the rat brain. Endocrinology, 102, 697–708 (1978)

    Google Scholar 

  • Pelletier, G., Dube, D.: Electron microscopic immunohistochemical localization of α-MSH in the rat brain. Am. J. Anat., 150, 201–206 (1977)

    Google Scholar 

  • Pelletier, G., Leclerc, R.: Immunohistochemical localization of adreno-corticotropin in the rat brain. Endocrinology, 104, 1426–1432 (1979)

    Google Scholar 

  • Rivier, C., Vale, W., Ling, N., Brown, M., Guillemin, R.: Stimulation in vivo of the secretion of prolactin and growth hormone by β-endorphin. Endocrinology, 100, 238–241 (1977)

    Google Scholar 

  • Roberts, J.L., Herbert, E.: Characterization of a common precursor to corticotropin and β-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule. Proc. Natl. Acad. Sci., 74, 4826–4830 (1977)

    Google Scholar 

  • Rossier, J., Vargo, T.M., Minick, S., Ling, N., Bloom, F.E., Guillemin, R.: Regional dissociation of β endorphin and enkephalin contents in rat brain and pituitary. Proc. Natl. Acad. Sci., 74, 5162–5165 (1977)

    Google Scholar 

  • Rubinstein, M., Stein, S., Udenfriend, S.: Characterization of pro-opiocortin, a precursor to opioid peptides and corticotropin. Proc. Natl. Acad. Sci., 75, 669–671 (1978)

    Google Scholar 

  • Seidah, N.G., Gianoulakis, C., Crine, P., Lis, M., Benjannet, S., Routhier, R., Chretien, M.: In vitro biosynthesis and chemical characterization of beta-lipotropin, gamma-lipotropin and beta-endorphin in rat pars intermedia. Proc. Natl. Acad. Sci., 75, 3153–3157 (1978)

    Google Scholar 

  • Sofroniew, M.V.: Immunoreactive β-endorphin and ACTH in the same neurons of the hypothalamic arcuate nucleus in the rat. Am. J. Anat., 154, 283–289 (1979)

    Google Scholar 

  • Toubeau, G.: Identification immunocytochimique de neurones contenant de l'ACTH 17–39 dans le cerveau du rat. C. R. Acad. Sci. (D) Paris, 287, 499–502 (1978)

    Google Scholar 

  • Tramu, G., Leonardelli, J., Dubois, M.P.: Immunohistochemical evidence for an ACTH-like substance in hypothalamic LH-RH neurons. Neurosci. Lett., 6, 305–309 (1977)

    Google Scholar 

  • Watson, S.J., Barchas, J.D., Li, C.H.: β-lipotropin: localization of cells and axons in rat brain by immunocytochemistry. Proc. Natl. Acad. Sci., 74, 5155–5158 (1977)

    Google Scholar 

  • Watson, S.J., Akil, H., Richard, C.W., Barchas, J.D.: Evidence for two separate opiate peptide neuronal systems. Nature, 275, 226–228 (1978)

    Google Scholar 

  • Zimmerman, E.A., Liotta, A., Krieger, D.T.: β-Lipotropin in brain: localization in hypothalamic neurons by immunoperoxidase technique. Cell Tissue Res., 186, 393–398 (1978)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The authors thank the following colleagues for providing compounds used in the present investigation: Prof. C.H. Li for human β-LPH; Prof. M. Herlant and Dr. C. Dessy for anti-β-LPH I.S.; Prof. L. Sternberger and Dr. M.P. Dubois for the PAP complex; Dr. C. Dessaules for ACTH and MSH; Prof. P. Czernichow, Drs. J. Legros and M.P. Dubois for anti-neurophysin, anti-oxytocin and antivasopressin. We also thank C. Jacquemard for technical assistance and D. Giammarco and O. Blandin for translating the manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bloch, B., Bugnon, C., Fellmann, D. et al. Neurons of the rat hypothalamus reactive with antisera against endorphins, ACTH, MSH and β-LPH. Cell Tissue Res. 204, 1–15 (1979). https://doi.org/10.1007/BF00235160

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00235160

Key words

Navigation