Discordant changes between immunoreactive ACTH and beta-endorphin in rat brain and pituitary during early development

Discordant changes in brain concentrations of immunoreactive (IR-) adrenocorticotropic hormone (ACTH) or beta-endorphin, peptides derived from pro-opiomelanocortin (POMC), have been reported during the latter part of development and with subsequent aging. These changes were believed to be due to age-related alterations in the regulation of metabolism of POMC-related peptides. However, concentrations of IR-ACTH and IR-beta-endorphin have not been simultaneously studied during early development when many changes in brain development and behavior are occurring. To determine whether concentrations of IR-ACTH and IR-beta-endorphin change during early development and whether changes are discordant, concentrations of IR-ACTH and IR-beta-endorphin were measured in several brain regions and pituitary in rats at 10, 29 and 80 days after birth. Whereas IR-ACTH in extrahypothalamic brain increased at day 29, and decreased at day 80, it did not change in hypothalamus and pituitary. Between day 10 and 29, IR-beta-endorphin rose in all brain regions, but subsequent changes in different tissues were variable at day 80. Because concentration changes can be mediated by alterations in one or more regulatory mechanisms, chromatographic profiles of hypothalamus and amygdala and molar ratios of all tissues were subsequently studied to give further insight into the mechanisms of the discordant changes. Molecular profiles of hypothalamic IR-ACTH and amygdalar IR-beta-endorphin exhibited lesser proportions of large molecular forms and greater proportions of ACTH and beta-endorphin during development. Molar ratios of IR-ACTH/IR-beta-endorphin in all tissues and ratios of ACTH1-39/beta-endorphin in hypothalamus and amygdala changed during development.

(1) changes in IR-ACTH and IR-beta-endorphin occur in rat pituitary and several brain regions at different ages during early development and are frequently discordant; (2) molecular profiles suggested that the activity of processing enzymes for POMC and its derivatives vary in hypothalamus and amygdala with respect to type of derivative, brain region, and developmental age; and (3) changes in some molecular profiles and changes in molar ratios of IR-ACTH/IR-beta-endorphin and ratios of ACTH1-39/beta-endorphin suggest that changes in processing and possibly changes in neurosecretion and degradation contribute to concentration changes independent of possible alterations in biosynthesis of POMC.