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.
KeywordsLuteinising Hormone Intermediate Lobe Lean Animal Hypothalamic Extract Gold Thioglucose
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