The hypothalamo — pituitary system in obesity
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.
KeywordsObesity Dopamine Corticosteroid Cortisol Testosterone
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- 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
- Bray, G. A. and York, D. A. (1971). Genetically transmitted obesity in rodents. Physiol. Rev., 51, 598–646Google Scholar
- 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
- Hems, D. A. (1979). This volumeGoogle Scholar
- 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
- 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
- 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
- Larsson, L. I. (1977). Corticotrophin-like peptides in central nerves and in endocrine cells of gut and pancreas. Lancet, ii, 1311–1323Google Scholar
- 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
- 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
- Migeon, C. J., Green, O. C. and Eckert, J. P. (1963). Study of adrenocortical function in obesity. Metabolism, 12, 718–739Google Scholar