Skip to main content
SpringerLink
Log in

Effects of MIF-I and TRH on the brain

  • Chapter
Hormones and the Brain

  • 86 Accesses

Abstract

MIF-I (prolyl-leucyl-glycinamide) and TRH (pyroglutamyl-histidyl-proline amide) have direct central nervous system effects in animals. In a series of double-blind, placebo and imipramine controlled studies in humans, MIF-I has shown promise as a rapidly acting antidepressant in a dose of approximately 1 mg/kg but not in doses of 0.1, 2 and 10mg/kg. MIF-I stimulates motor activity in monkeys with a similar curvilinear dose response curve. MIF-I is also reported to lower ACTH and may act in depression by decreasing activity of the hypothalamic—pituitary—adrenal axis known to be increased in depression. Because MIF-I potentiates the effects of dopa, it has been tried as a treatment in Parkinson’s disease with generally favourable results that suggest a curvilinear dose response curve. MIF-I has also been found to increase the sensitivity of animals to naloxone, to block the development of physical dependency on morphine and to reduce the effect of morphine on animals. Despite its early promise, TRH has not been found to be a clinically effective antidepressant in humans. However, the blunted TSH response to TRH in mental depression has diagnostic and prognostic value. The persistence of a blunted TSH response to TRH indicates a strong likelihood of early relapse, while the recovery of a normal TSH response is a good prognostic indication for continued recovery without maintenance therapy. Future indicated research with MIF-I and TRH is discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Barbeau, A. (1975). Potentiation of levodopa effect by intravenous 1-prolyl-1-leucyl-glycine amide in man. Lancet, 2, 683

    Article  PubMed  CAS  Google Scholar 

  • Bigelow, L. B., Gillen, J. C., Semal, S. and Wyatt, R. J. (1975). Thyrotropin-releasing hormone in chronic schizophrenia. Lancet, 2, 869

    Article  PubMed  CAS  Google Scholar 

  • Brambilla, F., Smeraldi, E., Sacchetti, E., Negri, F., Cocchi, D. and Müller, E. E. (1978). Deranged anterior pituitary responsiveness to hypothalamic hormones in depressed patients. Arch. Gen. Psychiat., 35, 1231

    PubMed  CAS  Google Scholar 

  • Breese, G. R., Cott, J. M., Cooper, B. R., Prange, A. J. and Lipton, M. A. (1974). Antagonism of ethanol narcosis by thyrotropin releasing hormone. Life Sci., 14, 1053

    Article  PubMed  CAS  Google Scholar 

  • Caraceni, T., Parati, E. A., Girotti, F., Celano, I., Frigerio, C., Cocchi, D. and Muller, E. E. (1979). Failure of MIF-I to affect behavioral responses in patients with Parkinson’s disease under l-dopa therapy. Psychopharmacology, 63, 217

    Article  PubMed  CAS  Google Scholar 

  • Carroll, B. J. and Mendels, J. (1976). Neuroendocrine regulation in affective disorders. In E. J. Sachar (ed.), Hormones, Behavior andPsychopathology, pp. 193–224. (New York: Raven Press)

    Google Scholar 

  • Chiu, S. and Mishra, R. K. (1979). Antagonism of morphine-induced catalepsy by l-prolyl-l-leucyl-glycinamide. Eur. J. Pharmacol., 53, 119

    Article  PubMed  CAS  Google Scholar 

  • Coppen, A., Peet, M., Montgomery, S. and Baily, J. (1975). Thyrotropin-releasing hormone in the treatment of depression. Lancet, 2, 433

    Google Scholar 

  • Cox, B., Kastin, A. J. and Schneider, H. (1976). A comparison between a melanocyte-stimulating hormone inhibitory factor (MIF-I) and substances known to activate central dopamine receptors.Eur. J. Pharmacol., 36, 141

    Article  PubMed  CAS  Google Scholar 

  • Crowley, T. J. and Hydinger, M. (1976). MIF, TRH and simian social and motor behavior. Pharmacol. Biochem. Behav., suppl. 1, 79

    Article  Google Scholar 

  • Davis, K. L., Hollister, L. E. and Berger, P. A. (1975). Thyrotropin-releasing hormone in schizophrenia. Am. J. Psychiat., 132, 951

    PubMed  CAS  Google Scholar 

  • Davis, K. L., Kastin, A. J., Beilstein, B. A. and Vento, A. L. (1980). MSH and MIF in animal models of tardive dyskinesia. Pharmacol. Biochem. Behav., 13, 37

    Article  PubMed  CAS  Google Scholar 

  • Ehrensing, R. H. and Kastin, A. J. (1978). Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression. Am. J. Psychiat, 135, 562

    PubMed  CAS  Google Scholar 

  • Ehrensing, R. H. and Kastin, A. J. (1977). TRH: clinical investigations for non-endocrine actions in man. In L. Martini and G. M. Besser (eds.), Clinical Endocrinology, pp. 133–142. (New York: Academic Press)

    Google Scholar 

  • Ehrensing, R. H. and Kastin, A. J. (1974). Melanocyte-stimulating hormone release inhibiting hormone as an anti-depressant. A pilot study. Arch. Gen. Psychiat., 30, 63

    PubMed  CAS  Google Scholar 

  • Ehrensing, R. H., Kastin, A. J., Larson, P. F. and Bishop, G. (1977). Melanocyte-stimulating hormone release inhibiting factor-I and tardive dyskinesia. Dis. Nerv. Syst., 38, 303

    PubMed  CAS  Google Scholar 

  • Ehrensing, R. H., Kastin, A. J., Schalch, D. S., Friesen, H., Vargas, R. and Schally, A. V. (1974). Affective state and thyrotropin and prolactin responses after repeated injections of thyro- tropin-releasing hormone in depressed patients.Am. J. Psychiat., 161, 714

    Google Scholar 

  • Fischer, P. A., Schneider, E., Jacobi, P. and Maxion, H. (1974). Effect of melanocyte-stimulating hormone release inhibiting factor (MIF) in Parkinson’s syndrome. Eur. J. Neurol., 12, 360

    Article  CAS  Google Scholar 

  • Friedman, E., Friedman, J. and Gershon, S. (1973). Dopamine synthesis: stimulation by a hypothalamic factor.Science, 182, 831

    Article  PubMed  CAS  Google Scholar 

  • Gerstenbrand, F., Poewe, W., Aichner, F. and Kozma, C. (1979). Clinical utilization of MIF-I. In Colluet al. (eds.), Central Nervous System Effects of Hypothalamic Hormones and Other Peptides, pp. 415–126. (New York: Raven Press)

    Google Scholar 

  • Gold, P. W., Goodwin, F. K., Wehr, T. and Repar, R. (1977). Pituitary thyrotropin response to thyrotropin-releasing hormone in affective illness: relationship to spinal fluid amine metabolites. Am. J. Psychiat., 134, 1028

    PubMed  CAS  Google Scholar 

  • Hall, R., Besser, G. M., Schally, A. V., Coy, D. H., Evered, D., Goldie, D. J., Kastin, A. J., McNeilly, A. S., Mortimer, C. H., Rhenekos, D., Turnbridge, W. M. G. and Weightman, D. (1973). Action of growth-hormone-release inhibitory ormone in healthy men and in acromegaly. Lancet, 2, 581

    Article  PubMed  CAS  Google Scholar 

  • Inanga, K., Nakano, T., Nagata, T., Tanaka, M. and Ogawa, N. (1978). Behavioural effects of protirelin in schizophrenia. Arch. Gen. Psychiat., 35, 1011

    Google Scholar 

  • Itil, T. M. (1976). Neurophysiological effects of hormones in humans: computer EEG profiles of sex and hypothalamic hormones. In E. J. Sachar (ed.), Hormones, Behavior and Psychopathology, pp. 31–40. (New York: Raven Press)

    Google Scholar 

  • Kastin, A. J. (1967). Letter to the editor. N. Engl. J. Med., 276, 1041

    Google Scholar 

  • Kastin, A. J. and Barbeau, A. (1972). Preliminary clinical studies with 1-prolyl-1-leucyl-glycine amide in Parkinson’s disease. Can. Med. Assoc. J., 107, 1079

    PubMed  CAS  Google Scholar 

  • Kastin, A. J., Coy, D. H., Schally, A. V. and Meyers, C. A. (1978a). Activity of VIP, somatostatin and other peptides in the mouse vas deferens assay. Pharmacol. Biochem. Behav., 9, 673

    Article  PubMed  CAS  Google Scholar 

  • Kastin, A. J., Ehrensing, R. H., Schalch, D. S. and Anderson, M. S. (1972). Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone.Lancet, 2, 740

    Article  PubMed  CAS  Google Scholar 

  • Kastin, A. J., Plotnikoff, N. P., Sandman, C. A., Spirtes, M. A., Kostrzewa, R. M., Paul, S. M., Stratton, L. O., Miller, L. H., Labrie, F., Schally, A. V. and Goldman, H. (1975). The effects of MSH and MIF on the brain. In W. E. Stumpf and L. D. Grant (eds.), Anatomical Neuro-endocrinology, pp. 290–297. (Basel: Karger)

    Google Scholar 

  • Kastin, A. J., Schally, A. V., Ehrensing, R. H. and Barbeau, A. (1974). Endocrine and extra-endocrine studies of hypothalamic hormones in man. In. K. Lederis and K. E. Cooper (eds.), Recent Studies of Hypothalamic Function, pp. 196–206. (Basel: Karger)

    Google Scholar 

  • Kastin, A. J., Scollan, E. L., Ehrensing, R. H., Schally, A. V. and Coy, D. H. (1978b). Enkephalin and other peptides reduce passiveness. Pharmacol. Biochem. Behav., 9, 515

    Article  PubMed  CAS  Google Scholar 

  • Kiely, W. F., Adrian, A. D., Lee, J. H. and Nicoloff, J. T. (1976). Therapeutic failure of oral thyrotropin-releasing hormone in depression. Psychosom. Med., 38, 233

    PubMed  CAS  Google Scholar 

  • Kirkegaard, C., BjØrum, N., Cohn, D. and Lauridsen, V. B. (1978). Thyrotropin-releasing hormone (TRH) stimulation test in manic-depressive illness. Arch. Gen. Psychiat., 35, 1017

    PubMed  CAS  Google Scholar 

  • Kirkegaard, C. and Smith, E. (1978). Continuation therapy in endogenous depression controlled by changes in the TRH stimulation test. Psychol. Med., 8, 501

    Article  PubMed  CAS  Google Scholar 

  • Kostrzewa, R. M., Kastin, A. J. and Sobrian, S. K. (1978). Potentiation of apomorphine action in rats by L-prolyl-L-leucyl-glycine amide. Pharmacol. Biochem. Behav., 9, 375

    Article  PubMed  CAS  Google Scholar 

  • Kostrzewa, R. M., Kastin, A. J. and Sprites, M. A. (1975). Alpha MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas. Pharmacol. Biochem. Behav., 3, 1017

    Article  PubMed  CAS  Google Scholar 

  • Loosen, P. T. and Prange, A. J. (1979). Behavioral changes in depression after TRH: antagonism by pre-treatment with thyroid hormones. Presented at the 10th International Congress of the Society for Psychoneuroendocrinology, August 8–11, Park City, Utah

    Google Scholar 

  • Loosen, P. T., Prange, A. J. and Wilson, I. C. (1979). TRH (protirelin) in depressed alcoholic men. Arch. Gen. Psychiat., 36, 540

    PubMed  CAS  Google Scholar 

  • Loosen, P. T., Prange, A. J. and Wilson, I. C. (1978). Influence of Cortisol on TRH-induced TSH response in depression. Am. J. Psychiat., 135, 244

    PubMed  CAS  Google Scholar 

  • Maeda, K., Kato, Y., Ohio, S., Chihard, K., Yoshimoto, Y., Yamaguchi, N., Kuromaru, S. and Imura, H. (1978). Growth hormone and prolactin release after injections of thyrotropin- releasing hormone in patients with depression. J. Clin. Endocrinol., 40, 501

    Article  Google Scholar 

  • Plotnikoff, N. P. and Kastin, A. J. (1974). Pharmacological studies with the tripeptide prolyl-1-leucyl-glycinamide. Arch. Int. Pharmacodyn., 211, 211

    PubMed  CAS  Google Scholar 

  • Plotnikoff, N. P., Kastin, A. J., Anderson, M. S. and Schally, A. V. (1973). Deserpidine antagonism by a tripeptide, 1 -prolyl- 1-leucyl-glycinamide. Neuroendocrinology, 11, 67

    Article  PubMed  CAS  Google Scholar 

  • Plotnikoff, N. P., Kastin, A. J., Anderson, M. S. and Schally, A. V. (1972a). Oxotremorine antagonism by a hypothalamic hormone, melanocyte-stimulating hormone release-inhibiting factor, MIF. Proc. Soc. Exp. Biol. Med., 140, 811

    PubMed  CAS  Google Scholar 

  • Plotnikoff, N. P., Kastin, A. J., Anderson, M. S. and Schally, A. V. (1971). DOPA potentiation by MIF. Life Sci., 10, 1279

    Article  CAS  Google Scholar 

  • Plotnikoff, N. P., Minard, F. N. and Kastin, A. J. (1974). Dopa potentiation in ablated animals and brain levels of biogenic amines in intact animals after prolyl-leucyl-glycinamide. Neuroendocrinology, 14, 271

    Article  PubMed  CAS  Google Scholar 

  • Plotnikoff, N. P., Prange, A. J., Bresse, G. R., Anderson, M. S. and Wilson, I. C. (1972b). Thyrotropin releasing hormone: enhancement of DOPA activity by a hypothalamic hormone. Science, 178, 417

    Article  PubMed  CAS  Google Scholar 

  • Prange, A. J., Bresse, G. R., Cott, J. M., Martin, B. R., Cooper, B. R., Wilson, I. C. and Plotnikoff, N. P. (1974). Thyrotropin-releasing hormone: antagonism in pentobarbitol in rodents. Life Sci., 14, 447

    Article  PubMed  CAS  Google Scholar 

  • Prange, A. J., Wilson, I. C., Lara, P. O., Alltop, L. B. and Breese, G. R. (1972). Effects of thyrotropin-releasing hormone in depression. Lancet, 2, 999

    Article  PubMed  Google Scholar 

  • van Ree, J. M. and de Wied, D. (1976). Prolyl-leucyl-glycinamide (PLG) facilitates morphine dependence. Life Sci., 19, 1331

    Article  PubMed  Google Scholar 

  • van Ree, J. M., de Wied, D., Bradbury, A. F., Hulme, E. C., Smyth, D. G. and Snell, C. R. (1976). Induction of tolerance to the analgesic action of lipoprotein C-fragment. Nature, 264, 792

    Article  PubMed  Google Scholar 

  • Spitzer, R. L., Endicott, J. and Robbins, E. (1978). Research diagnostic criteria—rationale and reliability. Arch. Gen. Psychiat., 35, 773

    PubMed  CAS  Google Scholar 

  • Stratton, L. O., Gibson, C. A., Kolar, K. G. and Kastin, A. J. (1976). Neonatal treatment with TRH affects development, learning and emotionality in the rat. Pharmacol. Biochem. Behav., 5 (suppl. 1), 65

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, S., Kondo, H., Yoshimura, M. and Ochi, Y. (1973). Thyrotropin response to TRH in depressive illness: relation of clinical subtypes and prolonged duration of depressive episode. Folia Psychiat. Neurol. Jpn., 28, 305

    Google Scholar 

  • Walter, R., Ritzmann, R. F., Bhargava, H. N. and Flexner, L. B. (1979). Prolyl-leucyl-glycinamide cyclo (leucylglycine) and derivatives block development of physical dependence on morphine in mice. Proc. Natl. Acad. Sci., USA, 76, 518

    Article  PubMed  CAS  Google Scholar 

  • Wilson, I. C., Lara, P. P. and Prange, A. J. (1973). Thyrotropin-releasing hormone in schizophrenia. Lancet. 2, 43

    Article  PubMed  CAS  Google Scholar 

  • Voigt, K. H., Fehm, H. L., Lang, R. E., Beinert, K. E. and Pfeiffer, E. F. (1977). Suppression of ACTH secretion by synthetic MSH-release inhibiting factor PRO-LEU-GYL-NH2 in Addison’s disease. Horm. Metab. Res., 9, 150

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Ochsner Clinic, 1514 Jefferson Highway, 70121, New Orleans, LA, USA

    Dr R. H. Ehrensing (Chairman)

Authors
  1. Dr R. H. Ehrensing
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Kastin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1980 MTP Press Limited

About this chapter

Cite this chapter

Ehrensing, R.H., Kastin, A.J. (1980). Effects of MIF-I and TRH on the brain. In: Hormones and the Brain. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-8709-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-8709-8_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-009-8711-1

  • Online ISBN: 978-94-009-8709-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation