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Effects of neurotransmitters on the release of corticotropin releasing hormone (CRH) by rat hypothalamic tissue in vitro

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Summary

Effects of neurotransmitters on in vitro release of CRH from rat hypothalamic tissue were investigated. Three whole hypothalami or three mediobasal hypothalami from male rats, adrenalectomized 7 days before, were incubated for 10 min in a medium similar to cerebrospinal fluid at 37 ° C under 95% O2, 5% CO2. CRH activity was assayed by radioimmunological measurement of ACTH released by isolated pituitary cells from adrenalectomized rats.

Norepinephrine (NE) at a concentration of 0.02×10−6 M to 2×10−6 M stimulated dose-related CRH release. At larger concentrations the response decreased again (bell-shaped dose-response relationship). The action of norepinephrine was completely blocked by coincubation with phentolamine. Similar results were obtained whether whole hypothalami or mediobasal hypothalami were incubated with norepinephrine. This suggests that the site of action of NE was within the mediobasal hypothalamus. The possibility that the observed effects were due to the CRH-like activity of vasopressin released from the hypothalamic tissue was excluded by simultaneous measurements of CRH activity and arginine-vasopressin concentrations in the medium. Dopamine at very large concentrations (17.6×10−6 M) also stimulated CRH release. Acetylcholine, serotonin, histamine and GABA did not influence the basal CRH release at any of the concentrations tested.

These results suggest that in the rat, norepinephrine may have a physiological role as stimulator of CRH-release at the level of the mediobasal hypothalamus. However, in view of the conflicting results obtained with similar and other methods, no definite conclusions should yet be drawn.

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References

  • Abe K, Hiroshige T (1974) Changes in plasma corticosterone and hypothalamic CRF levels following intraventricular injection or drug-induced changes of brain biogenic amines in the rat. Neuroendocrinology 14: 195–211

    Google Scholar 

  • Bhattacharya AN, Marks BH (1970) Effects of α-methyl-tyrosine and p-chlorphenylalanine on the regulation of ACTH secretion. Neuroendocrinology 6: 49–54

    Google Scholar 

  • Bigdeli H, Snyder PJ (1978) Gonadotropin-releasing hormone release from the rat hypothalamus: dependence on membrane depolarization and calcium influx. Endocrinology 103: 281–286

    Google Scholar 

  • Bradbury MWB, Burden J, Hillhouse EW. Jones MT (1974) Stimulation electrically and by acetylcholine of the rat hypothalamus in vitro. J Physiol (Lond) 239: 269–283

    Google Scholar 

  • Bridges TE, Hillhouse EW, Jones MT (1976) The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro. J Physiol (Lond) 260: 647–666

    Google Scholar 

  • Cuello AC, Shoemaker WJ, Ganong WF (1974) Effect of 6-hydroxydopamine on hypothalamic norepinephrine and dopamine content, ultrastructure of the median eminence and plasma corticosterone. Brain Res 78: 57–69

    Google Scholar 

  • Edwardson JA, Bennet GW (1974) Modulation of corticotrophin-releasing factor release from hypothalamic synaptosomes. Nature 251: 425–427

    Google Scholar 

  • Eggena P, Polson AX (1974) Osmotic stimulaion of vasotocin secretion by the toad's hypothalamo-neurohypophyseal system in vitro. Endocrinology 94: 35–44

    Google Scholar 

  • Eisenberg RM (1975) Further evidence of a central alpha-adrenergic inhibitory influence on the hypothalamo-pituitaryadrenal axis in the rat. Neuroendocrinology 17: 154–166

    Google Scholar 

  • Ganong WF (1972) Evidence for a central noradrenergic system that inhibits ACTH secretion. In: Knigge KM et al. (eds) Brain-endocrine interaction. Median eminence: Structure and function. Int Symp Munich 1971. Karger, Basel, pp 254–266

    Google Scholar 

  • Hillhouse EW, Burden JL, Jones MT (1975) The effect of various putative neurotransmitters on the release of corticotrophin releasing hormone from the hypothalamus of the rat in vitro. 1. The effect of acetylcholine and noradrenaline. Neuroendocrinology 17: 1–11

    Google Scholar 

  • Hillhouse EW, Jones MT (1976) Effect of bilateral adrenalectomy and corticosteroid therapy on the secretion of corticotrophinreleasing factor activity from the hypothalamus of the rat in vitro. J Endocrinol 71: 21–30

    Google Scholar 

  • Hirsch GH, Moore KE (1968) Brain catecholamines and the reserpine-induced stimulation of the pituitary-adrenal system. Neuroendocrinology 3: 398–405

    Google Scholar 

  • Jones MT, Hillhouse EW, Burden J (1976a) Effect of various putative neurotransmitters on the secreton of corticotrophin-releasing hormone from the rat hypothalamus in vitro — a model of the neurotransmitter involved. J Endocrinol 69: 1–10

    Google Scholar 

  • Jones MT, Hillhouse EW, Burden JL (1976b) Secretion of corticotrophin-releasing hormone in vitro. In: Martini L, Ganong WF (eds) Frontiers in neuroendocrinology. Raven Press, New York (vol 4, pp 195–226)

    Google Scholar 

  • Jones MT, Gillham B, Hillhouse EW (1977a) The nature of corticotrophin-releasing factor from the rat hypothalamus in vitro. Fed Proc 36: 2104–2109

    Google Scholar 

  • Jones MT, Hillhouse EW, Burden JL (1977b) Structure-activity relationships of corticosteroid feedback at the hypothalamic level. J Endocrinol 74: 415–424

    Google Scholar 

  • Jones MT, Hillhouse EW (1977) Neurotransmitters regulation of corticotrophin-releasing factor in vitro. In: Krieger DT, Ganong WF (eds) ACTH and related peptides: Structure, regulation and action. New York Academy of Sciences, New York, pp 536–560

    Google Scholar 

  • Kaneko M, Hiroshige T (1978) Site of fast, rate-sensitive feedback inhibition of adrenocorticotrophin secretion during stress. Am J Physiol 234: R46-R51

    Google Scholar 

  • Kaplanski J, Delft AML van, Nyakas C, Stoof JC, Smelik PG (1974) Circadian periodicity and stress responsiveness of the pituitary-adrenal system of rats after central administration of 6-hydroxydopamin. J Endocrinol 63: 299–310

    Google Scholar 

  • Krieger DT (1975) Effect of intraventricular neonatal 6-OH-dopamine or 5,6-dihydroxytryptamine administration on the circadian periodicity of plasma corticosteroid levels in the rat. Neuroendocrinology 17: 62–74

    Google Scholar 

  • Krieger DT, Krieger HP (1970) Effect of dexamethasone on pituitary-adrenal activation following intrahypothalamic implantation of “neurotransmitters”. Endocrinology 87: 179–182

    Google Scholar 

  • Lang RE, Voigt KH, Fehm HL, Pfeiffer EF (1974) A sensitive CRF-assay; Radioimmunological measurement of ACTH secreted by rat anterior pituitary cell suspension. In: Levine R, Pfeiffer EF (eds) Radioimmunoassay: Methodology and applications in physiology and in clinical studies. Thieme, Stuttgart, pp 66–72

    Google Scholar 

  • Lippa AS, Antelman SM, Fahringer, EE. Redgate ES (1973) Relationship between catecholamines and ACTH: effects of 6-hydroxy-dopamine. Nature N Biol 241: 24–25

    Google Scholar 

  • Marantz R. Sachar EJ, Weitzman E, Sassin J (1976) Cortisol and GH responses to D- and L-amphetamine in monkeys. Endocrinology 99: 459–465

    Google Scholar 

  • Rees L, Butler PWP, Gosling C, Besser GM (1970) Adrenergic blockade and the corticosteroid and growth hormone responses to methylamphetamine. Nature 228: 565–566

    Google Scholar 

  • Rose JC, Goldsmith PC, Holland FJ, Kaplan SL, Ganong WF (1976) Effect of electrical stimulation of the canine brain stem on the secretion of ACTH and growth hormone (GH). Neuroendocrinology 22: 352–362

    Google Scholar 

  • Rotsztejn WH, Charli JL, Patton E, Epelbaum J, Kordon C (1976) In vitro release of luteinizing hormone-releasing hormone (LHRH) from rat mediobasal hypothalamus: effects of potassium, calcium and dopamine. Endocrinology 99: 1663–1666

    Google Scholar 

  • Rotsztejn WH, Charli JL. Patton E. Kordon C (1977) Stimulation by dopamine of luteinizing hormone-releasing hormone (LHRH) release from the mediobasal hypothalamus in male rats. Endocrinology 101: 1475–1483

    Google Scholar 

  • Scapagnini U, Loon GR van, Moberg GP, Preziosi P, Ganong WF (1972) Evidence for central norepinephrine-mediated inhibition of ACTH secretion in the rat. Neuroendocrinology 10: 155–160

    Google Scholar 

  • Scapagnini U, Annunziato L., Lombardi G. Oliver Ch. Preziosi P (1975) Time-course of the effect of α-methyl-p-tyrosine on ACTH secretion. Neuroendocrinology 18: 272–276

    Google Scholar 

  • Sladek CD, Joynt JR (1979) Angiotensin stimulation of vasopressin release from the rat hypothalamo-neurohypophyseal system in organ culture. Endocrinology 104: 148–153

    Google Scholar 

  • Toivola PTK, Gale CC (1972) Stimulation of growth hormone release by microinfusion of norepinephrine into hypothalamus of baboons. Endocrinology 90: 895–902

    Google Scholar 

  • Ulrich RS, Yuweiler A (1973) Failure of 6-hydroxydopamine to abolish the circadian rhythm of serum corticosterone. Endocrinology 92: 611–614

    Google Scholar 

  • Van Loon GR, Scapagnini U, Moberg GP. Ganong WF (1971) Evidence for central adrenergic neural inhibition of ACTH secretion in the rat. Endocrinology 89: 1464–1469

    Google Scholar 

  • Voigt KH, Fehm HL, Pfeiffer EF (1971) Production of antibodies to ACTH for use in radioimmunoassay. Horm Metab Res 3: 313–317

    Google Scholar 

  • Wagner H, Häberle H, Maier V, Lang RE (1978) Transmitter mediated arginine vasopressin release from superfused hypothalamus and pituitary gland. J Endocrinol Invest 1: 215–220

    Google Scholar 

  • Weiner RI, Ganong WF (1978) Role of brain monoamines and histaraine in regulation of anterior pituitary secretion. Physiol Revs 58: 905–959

    Google Scholar 

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Authors and Affiliations

  1. Abteilung Innere Medizin I, Zentrum für Innere Medizin und Kinderheilkunde, Universität Ulm, Steinhövelstr. 9, D-7900, Ulm, Federal Republic of Germany

    H. L. Fehm, R. E. Lang & E. F. Pfeiffer

  2. Abteilung Physiologie I, Zentrum für Theoretische Medizin und Biologie, Universität Ulm, D-7900, Ulm, Federal Republic of Germany

    K. H. Voigt

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  1. H. L. Fehm
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  2. K. H. Voigt
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  3. R. E. Lang
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  4. E. F. Pfeiffer
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This work was supported by Deutsche Forschungsgemeinschaft. Bonn-Bad Godesberg. SFB 87/B2. K.H. V. is a recipient of a Heisenberg Stipendium

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Fehm, H.L., Voigt, K.H., Lang, R.E. et al. Effects of neurotransmitters on the release of corticotropin releasing hormone (CRH) by rat hypothalamic tissue in vitro. Exp Brain Res 39, 229–234 (1980). https://doi.org/10.1007/BF00237553

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