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

The accumulation of immunoreactive ACTH (ACTH_i), αMSH (αMSH_i), and _γ-lipotropin (_γLPH_i) 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, αMSH_i, and γLPHi increased with age. In the MBH, the increase occurred in such a manner that the molar ratio of _αMSH_i to ACTH_i remained constant regardless of the age of the animals. In contrast, in the POA and thalamus, the increase occurred disproportionately in favor of _αMSH_i, and thus the molar ratio of _αMSHi to ACTH_i was 3 times higher in the adult (120 days old) than in the young (10 or 21 days old) animals. Nevertheless, the ratio of (ACTH_i plus αMSH_i) to _γLPH_i 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 ACTHU-39), and 4.5K ACTH as ACTH-(l-39). Regardless of 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 ACTH_i. However, the predominant form of ACTH_i 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 _α MSH in the brain of the maturing rat.