Origin of immunoreactive ACTH in brain sites outside the ventral hypothalamus

Immunoreactive adrenocorticotropin (IR-ACTH) is widely distributed throughout the brain. Highest concentrations have been localized in the ventral hypothalamus, a recognized site of origin of IR-ACTH containing neuronal cell bodies. To determine whether IR-ACTH arises in other brain sites, we determined the effect on the concentration of IR-ACTH in several regions of rat brain after intracerebroventricular injection of colchicine, an agent that inhibits axoplasmic transport and leads to an accumulation of neuronal secretory products within cell bodies. Three regions (ventral hypothalamus, dorsal hypothalamus, amygdala) showed a significant increase in concentration of IR-ACTH after colchicine, whereas the hippocampus and preoptic area did not. Because neuropeptides, in general, undergo posttranslational processing during axoplasmic transport, it could be predicted that inhibition of transport would lead to a relative increase in 'large', precursor forms of hormone in regions containing cells of origin of neuropeptide tracts. Therefore, the effect of colchicine on the processing of molecular forms of IR-ACTH was also examined. In brain regions showing a significant increase in IR-ACTH after colchicine, the proportion of 'big' ACTH and ACTH1-39 (relative to total IR-ACTH) increased and the proportion of 'small' ACTH (less than 4,500 daltons) declined. In contrast, size distribution of IR-ACTH species in other areas were either the opposite or were unchanged. These studies indicate that in addition to the ventral hypothalamus, IR-ACTH also originates in the dorsal hypothalamus and the amygdala, and that decreased axoplasmic peptide transport is associated with decreased processing of molecular forms.