The limited data currently available are consistent with the view that melanocor-tins act as regulative factors in controlling food intake in humans. Autosomal recessive mutations that interfere with POMC expression have been reported to result in early onset of obesity, together with red hair color (suggesting a role for melanocortins in hair pigmentation in humans), and in deficiency of adrenal corticoid synthesis as a result of defective ACTH biosynthesis. A decrease in the activity of prohormone convertase 1 (PC 1; an important enzyme in POMC processing) has been reported in a woman with childhood obesity and a mutation of the PC 1 gene. This patient exhibited several endocrine abnormalities, including adrenal insufficiency, hypogonadotrophic hypogonadism, impaired glucose tolerance and reactive hypoglycemia, presumably due to impaired processing of POMC and proinsulin.
In addition, systemic application of MSH produces anti-inflammatory and antipyretic effects. Among the melanocortins, a-MSH is one of the most potent endogenous antipyretic agents inhibiting IL-1-induced fever. Centrally administered alpha-MSH can induce antipyretic effects.
It has been shown that MSH exerts strong anti-inflammatory activity via direct action on peripheral host cells:
• inhibition of descending neurogenic anti-inflammatory pathways arising from central nervous melanocortin receptors sites;
• local actions on receptors that control inflammation within the brain.
Since glia can secrete alpha-MSH and express melanocortin receptors, the effects of alpha-MSH on both fever and inflammation in the brain might be associated with the activation of glial cells.
To date, there are no clear indications for a role of MSH in neurodegenerative diseases or in neurological disorders. However, there is pharmaceutical evidence that MC-4 receptor antagonists could have a role in depression.
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