ADRENALECTOMY-INDUCED INCREASE OF BRAIN PROTEIN-SYNTHESIS IS ANTAGONIZED BY CORTICOSTERONE REPLACEMENTS IN FREE-MOVING RATS

The autoradiographic method with L-[S-35]-methionine was used to deter mine whether changes in glucocorticoid circulating levels were associa ted with changes in local rates of protein synthesis in rat brain. Chr onic bilateral adrenalectomy induced an increase of methionine incorpo ration rates into proteins in 60 of the 62 brain regions examined (mea n effect, +50%). This effect was confirmed biochemically and quantifie d by correcting for the relative contribution of methionine derived fr om protein degradation to the precursor pool for protein synthesis in the whole brain. Acute or chronic administration of corticosterone, at doses that normalize basal levels of adrenocorticotrophic hormone, re versed or prevented the adrenalectomy-induced increase of protein synt hesis in most regions. However, in nearly all the regions studied (59 of 62), acute corticosterone administration to sham-operated rats did not change the apparent rate of protein synthesis. These results demon strate that glucocorticoids exert a generalized inhibitory action on b rain protein synthesis, because the stimulatory and persistent effect of adrenalectomy on protein synthesis was antagonized by corticosteron e replacements at physiological doses. Thus, the regulation of overall brain protein synthesis by glucocorticoids emphasizes the role of neu roendocrine events on long-term neurochemical processes.