Modulators, Mediators, and Specifiers in Brain Function

Margules, D L, Margules, D. L., D. L. Margules

The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.