Molecular-weight profiles of immunoreactive corticotropin in the hypothalamus of the aging rat

Extracts of the medial basal hypothalamus (MBH), the preoptic anterior hypothalamus (POA), or the pituitary gland of young (4-month-old) and old (18-month-old) female rats were fractionated on columns of Sephadex G-75 superfine. Five forms of immunoreactive corticotropin (ACTH_i) were found in the MBH or POA: >40K, 30-40K, 20-30K, 5.7K, and 4.5K. In contrast, 4 forms of ACTH_i were found in the pituitary gland: 30-40K, 20-30K, 5.7K, and 4.5K. Thus, hypothalamic tissue contains a large form of ACTH (>40K ACTH) which is not present in the pituitary gland. We tentatively identified >40K ACTH as a large form of pro-opiocortin, 30-40K ACTH as pro-opiocortin, 20-30K ACTH as ACTH biosynthetic intermediate, 5.7K ACTH as glycosylated ACTH 1-39, and 4.5K ACTH as ACTH 1-39. The content of ACTH_i in the MBH and POA of old rats was lower than that of young rats. Nevertheless, regardless of the age of the animals, the fractional amount of 30-40K ACTH_i was high in the MBH (a region that includes the presumed site of biosynthesis of pro-opiocortin^5,19,22,27) compared to that in the POA (a region that is distant to the site of biosynthesis of pro-opiocortin). Moreover, the reduced fractional amount of 30-40K ACTH_i in the POA was associated with an increased fractional amount of >40K, 20-30K, 5.7K, and 4.5K ACTH_i. These findings are consistent with a precursor-product relationship between the 30-40K ACTH_i and 20-30K ACTH_i, 5.7K ACTH_i, and 4.5K ACTH_i. The possibilty that >40K ACTH_i is a metabolite of 30-40K ACTH_i,or that it is a large form of pro-opiocortin, the processing of which differs from that of the 30-40K ACTH_i, was considered. We propose that aging causes a decline in the production of pro-opiocortin, and that this decline is not accompanied by major changes in the processing of pro-opiocortin.