A Reduction in the Concentration of Immunoreactive Corticotropin, Melanotropin and Lipotropin in the Brain of the Aging Rat

We have previously shown that the hypothalamic concentration of immunoreactive alpha-melanotropin (alpha-MSHi) is markedly lower in the aging female rat than in the young rat. The current view is that alpha-MSH is derived from corticotropin (ACTH), and ACTH, in turn, is derived from a large molecular-weight precursor (pro-opiocortin); pro-opiocortin also serves as the precursor to beta- and gamma-lipotropin (LPH). To ascertain if the age-related reduction in the concentration of alpha-MSHi may be a result of a decline in the production of pro-opiocortin, we determined the content of immunoreactive ACTH (ACTHi), alpha-MSH (alpha-MSHi), gamma-LPH (gamma-LPHi), and protein, in 3 regions of the brain of young (4 months) and old (26-28 months) female rats: the medial basal hypothalamus (MBH, the region containing the perikarya of the ACTH/MSH/LPH neurons), the preoptic anterior hypothalamus (POA), and the thalamus (regions containing axons of these neurons). The concentration of ACTHi, alpha-MSHi (mol/mg protein), or gamma-LPHi (U/mg protein) in the MBH of old rats was 30-50% of that in the MBH of young rats. Moreover, the concentration of ACTHi, alpha-MSHi or gamma-LPHi in the POA and thalamus of old rats was also lower than that in the POA and thalamus of young rats. Based on these findings, we propose that aging causes a reduction in the production of pro-opiocortin in the brain of the female rat and that such a change may be related to the altered function of the brain of the aged.