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The hypothalamo — pituitary system in obesity

  • J. A. Edwardson
  • Amanda Donaldson

Summary

The widespread metabolic and endocrine abnormalities of obesity involve changes in pituitary function. In the genetically obese (ob/ob) mouse there are disturbances in secretion of all the known pituitary anterior lobe and intermediate lobe hormones.

There is increased secretion of corticotrophin (ACTH) by the anterior pituitary of ob/ob animals, and also of two related peptides, corticotrophin-like intermediate lobe peptide (CLIP) and melanophore-stimulating hormone (MSH) by the pars intermedia. Increased release of ACTH presumably accounts for the adrenal hypertrophy and elevated glucocorticoid levels observed in the ob/ob mouse. Evidence is described showing that CLIP, the free 18–39 COOH terminal fragment of ACTH, has insulin-releasing properties. The increased secretion of CLIP in the ob/ob mouse may be implicated in the development of hyperinsulinaemia.

In contrast to the corticotrophin-related peptides, there is evidence suggesting diminished secretion of gonadotrophins (FSH and LH), thyrotrophin (TSH), growth hormone (GH) and prolactin (PRL). In some cases this is associated with changes in levels of the appropriate hypothalamic releasing or release-inhibiting hormones.

These widespread changes indicate some biochemical defect at hypothalamic or higher level, perhaps in the neurotransmitter systems which regulate release of the hypophysiotropic peptides. Dopamine and noradrenaline levels are raised in the ob/ob mouse, but there is, as yet, no indication of the way in which impaired monoaminergic mechanisms could produce the characteristic abnormalities of pituitary secretion in this strain.

Keywords

Luteinising Hormone Intermediate Lobe Lean Animal Hypothalamic Extract Gold Thioglucose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Beevor, S., Beloff-Chain, A., Bogdanovic, S., Donaldson, A., Edwardson, J. A. and Hawthorn, J. (1979). Corticotrophin-like peptides, insulin secretion and obesity. Submitted to Nature Beloff-Chain, A. (1979). This volumeGoogle Scholar
  2. Bray, G. A. and York, D. A. (1971). Genetically transmitted obesity in rodents. Physiol. Rev., 51, 598–646Google Scholar
  3. Edwardson, J. A. and Donaldson, A. (1979). Regulation of corticotrophin-related peptides in the intermediate lobe and their possible relation to obesity. In The Interaction within the Brain-Pituitary-Adrenocortical System (ed. M. T. Jones, M. F. Dallman and B. Gillham, Academic Press, London (in press)Google Scholar
  4. Edwardson, J. A. and Hough, C. A. M. (1975). The pituitary adrenal system of the genetically obese (ob/ob) mouse. J. Endocrinol., 65, 99–107CrossRefGoogle Scholar
  5. Garces, L. Y., Kenny, F. M., Drash, A. and Taylor, F. H. (1968). Cortisol secretion rate during fasting of obese adolescent subjects. J. Clin. Endocrinol. Metab., 28, 1843–1847CrossRefGoogle Scholar
  6. Hems, D. A. (1979). This volumeGoogle Scholar
  7. Herbai, G. (1970). Weight loss in obese-hyperglycaemic and normal mice following trans- auricular hypophysectomy by a modified technique. Acta Endocrinol., 65, 712–722Google Scholar
  8. Joosten, H. F. P. and van der Kroon, P. H. W. (1974). Role of the thyroid in the development of the obese-hyperglycaemic syndrome in mice (oblob). Metabolism, 23, 425–436CrossRefGoogle Scholar
  9. Kahn, C. R. (1976). Insulin sensitivity and insulin resistance: regulation of insulin receptors in vivo. In Cell Membrane Receptors for Viruses, Antigens and Antibodies, Polypeptide Hormones and Small Molecules, Miles International Symposium Number 9 (ed. R. F. Beers and E. G. Bassett ), Raven Press, New York, pp. 33–46Google Scholar
  10. Kalucy, R. S., Crisp, A. H., Chard, T., McNeilly, A., Chen, C. N. and Lacey, J. H. (1976). Nocturnal hormonal profiles in massive obesity, anorexia nervosa and normal females. J. Psychosom. Res., 20, 595–604CrossRefGoogle Scholar
  11. Kley, H. K., Herberg, L. and Krueskemper, H. L. (1976). Measurement of urinary free corticosterone as a method for evaluating the adrenal function of small laboratory rodents. Acta Endocrinol., 82, Suppl. 202, 45–46Google Scholar
  12. Larsson, L. I. (1977). Corticotrophin-like peptides in central nerves and in endocrine cells of gut and pancreas. Lancet, ii, 1311–1323Google Scholar
  13. Larsson, L. I. (1978). Distribution of ACTH-like immunoreactivity in rat brain and gastrointestinal tract. Histochemistry, 55, 225–228CrossRefGoogle Scholar
  14. Lebovitz, H. E. (1973). In Methods in Investigative and Diagnostic Endocrinology, Vol. 2A (ed. S. A. Berson and R. S. Yallow), North-Holland, Amsterdam, pp. 349–359Google Scholar
  15. Lorden, J. F. and Oltmans, G. A. (1977). Hypothalamic and pituitary catecholamine levels in genetically obese mice (ob/ob). Brain Res., 131, 162–166CrossRefGoogle Scholar
  16. Lorden, J. F., Oltmans, G. A. and Margules, D. L. (1975). Central catecholamine levels in genetically obese mice (ob/ob and db/db). Brain Res., 96, 390–394CrossRefGoogle Scholar
  17. Lorden, J. F., Oltmans, G. A. and Margules, D. L. (1976). Central catecholamine turnover in genetically obese mice (ob/ob). Brain Res., 117, 357–361CrossRefGoogle Scholar
  18. Lowry, P. J. and Chadwick, A. (1970). Purification and amino-acid sequence of melanocyte- stimulating hormone from the dogfish, Squalus acanthias. Biochem. J., 118, 713–718CrossRefGoogle Scholar
  19. Luton, J. P., Thieblot, P., Valcke, J.-C., Mahoudeau, J. A. and Bricaire, H. (1977). Reversible gonadotrophin deficiency in male Cushing’s disease. J. Clin. Endocrinol. Metab., 45, 488–495CrossRefGoogle Scholar
  20. McCann, S. M., Fawcett, C. P. and Krulich, L. (1974). Hypothalamic hypophysial releasing and inhibiting hormones. In Endocrine Physiology, MTP International Review of Science, Physiology Series One, Vol. 5 (ed. S. M. McCann), Butterworths, London, pp. 31.-65Google Scholar
  21. Mains, R. E., Eipper, B. A. and Ling, N. (1977). Common precursor to corticotropins and endorphins. Proc. Nat. Acad. Sci. USA, 74, 3014–3018CrossRefGoogle Scholar
  22. Migeon, C. J., Green, O. C. and Eckert, J. P. (1963). Study of adrenocortical function in obesity. Metabolism, 12, 718–739Google Scholar
  23. Naeser, P. (1973). Adrenal function in the obese hyperglycaemic syndrome (ob/ob) in mice. Diabetologia, 9, 83CrossRefGoogle Scholar
  24. Patel, Y. C., Cameron, D. P., Stefan, Y., Malaisse-Lagae, F. and Orci, L. (1977). Somato-statin: widespread abnormality in tissues of spontaneously diabetic mice. Science, 198, 930–931CrossRefGoogle Scholar
  25. Scott, A. P., Ratcliffe, J. G., Rees, L. H., Landon, J., Bennett, H. P. J., Lowry, P. J. and McMartin, G. (1973). Pituitary peptide. Nature New BioL, 244, 65–67CrossRefGoogle Scholar
  26. Sinha, Y. N., Salocks, C. B. and Vanderlaan, W. P. (1975). Prolactin and growth hormone secretion in chemically induced and genetically obese mice. Endocrinology, 97, 1386–1393CrossRefGoogle Scholar
  27. Solomon, J. and Mayer, J. (1973). The effect of adrenalectomy on the development of the obese hyperglycemic syndrome in ob/ob mice. Endocrinology, 93, 510–513CrossRefGoogle Scholar
  28. Swerdloff, R. S., Batt, R. A. and Bray, G. A. (1976). Reproductive hormonal function in the genetically obese (ob/ob) mouse. Endocrinology, 98, 1359–1364CrossRefGoogle Scholar
  29. Tilders, F. J. H. and Smelik, P. G. (1977). Direct neural control of MSH secretion in mammals: the involvement of dopaminergic tubero-hypophysial neurones. Front. Horm. Res., 4, 80–93CrossRefGoogle Scholar
  30. Wykes, A. A., Christian, J. E. and Andrews, F. N. (1958). Radioiodine concentration and thyroid weight in normal, obese and dwarf strains of mice. Endocrinology, 62, 535–538CrossRefGoogle Scholar

Copyright information

© The Medical Research Council 1979

Authors and Affiliations

  • J. A. Edwardson
    • 1
  • Amanda Donaldson
    • 1
  1. 1.Department of PhysiologySt. George’s Hospital Medical SchoolLondonUK

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