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Posttranslational processing of proadrenocorticotropin/endorphin-derived peptides during postnatal development in the
Abstract:
The anterior pituitary content of pro-ACTH/endorphin-related peptides increased 5-fold from birth to 4 weeks and increased another 3-fold by adulthood. In contrast, the neurointermediate lobe content of pro-ACTH/endorphin-related peptides increased 15-fold from birth to 4 weeks and another 10-fold by adulthood. Despite the dramatic increase in content, posttranslational processing of pro-ACTH/endorphin in the neurointermediate lobe of the neonate closely resembled intermediate lobe processing in the adult; alpha MSH- and beta-endorphin-sized molecules (rather than ACTH and beta-lipotropin) accounted for more than 90% of the immunoreactivity in both neonates and adults. In the neurointermediate pituitary of both the neonate and the adult, the alpha MSH-sized material was largely diacetylated, and the beta-endorphin was both alpha-N-acetylated and C-terminally shortened. However, the extent of C-terminal shortening of beta-endorphin in the neurointermediate lobe of the neonate was not as great as that observed by postnatal day 21 or that in the adult. In the anterior pituitary, distinct differences in processing occurred between birth and adulthood. Proteolytic processing of pro-ACTH/endorphin was not as extensive on day 1 as in the adult, and pro-ACTH/endorphin accounted for 40-50% of the total immunoreactive peptide. The extent of processing of precursor increased around day 21, and a higher percentage of ACTH-(1-39) and beta-endorphin-(1-31)-sized material was found. Neonatal anterior pituitary contained substantial amounts of alpha MSH-sized material, whereas in adult anterior pituitary, less than 1-2% of the ACTH-related material was alpha MSH-sized. Despite these differences in the extent of proteolytic processing, neonatal anterior pituitary corticotropes resembled those of adults, in that they did not alpha-N-acetylate beta-endorphin or alpha MSH. Immunocytochemical studies demonstrated that a subset of the neonatal anterior pituitary corticotropes produced alpha MSH-related molecules.