Disproportionate accumulation of immunoreactive corticotropin, melanotropin, and lipotropin in the brain of the maturing rat.

Abstract

The accumulation of immunoreactive ACTH (ACTHi), alpha MSH (alpha MSHi), and gamma-lipotropin (gamma LPHi) as a function of age (10-120 days) was determined in three regions of the brain of male rats: the medial basal hypothalamus (MBH), the preoptic anterior hypothalamus (POA), and the thalamus. In each region of the brain, the concentrations of ACTHi, alpha MSHi, and gamma LPHi increased with age. In the MBH, the increase occurred in such a manner that the molar ratio of alpha MSHi to ACTHi remained constant regardless of the age of the animals. In contrast, in the POA and thalamus, the increase occurred disproportionately in favor of alpha MSHi, and thus the molar ratio of alpha MSHi to ACTHi was 3 times higher in the adult (120 days old) than in the young (10 or 21 days old) animals. Nevertheless, the ratio of (ACTHi plus alpha MSHi) to gamma LPHi was constant at a level of about 2 regardless of the age of the animal or the region of the brain. Extracts of the MBH or POA were fractionated on columns of Sephadex G-75 superfine. The gel filtration profiles of ACTHi were indicative of the presence of five molecular weight forms of ACTH: greater than 40K, 30-40K, 20-30K, 5.7K, and 4.5K. We tentatively identified greater than 40K ACTH as a large form of proopiocortin, 30-40K ACTH as proopiocortin, 20-30K ACTH as ACTH biosynthetic intermediate, 5.7K as glycosylated ACTH(1-39), and 4.5K ACTH as ACTH-(1-39). Regardless of the age of the animals, the fractional amount of 30-40K ACTH the age of the animals, the fractional amount of 30-40K ACTH was high in the MBH compared to that in the POA. Moreover, the small fractional amount of 30-40K ACTH in the POA was associated with a large fractional amount of small molecular weight forms of ACTHi. However, the predominant form of ACTHi in the POA changed with age: 20-30K ACTH was the major form in the young, whereas 4.5K ACTH was the major form in the adult. These results support the proposal that the production of proopiocortin increases with age, and there is enhanced processing of proopiocortin to ACTH-(1-39) and alpha MSH in the brain of the maturing rat.