Prenatal processing of pro-opiomelanocortin in the brain and pituitary of mouse embryos.

The processing of pro-opiomelanocortin (POMC) to ACTH- (adrenocorticotropin), MSH- (melanotropin) and endorphin-related peptides was studied in mouse embryos with the ultimate aim of determining the role of the POMC-related peptides in early development especially in the CNS. Mouse embryos at gestational days 10.5, 11.5, 12.5 and 14.5 were analyzed for POMC-derived peptides by SDS-PAGE, HPLC and radioimmunoassay using antisera specific for various regions of the prohormone. At embryonic day 10.5 (E 10.5) the prohormone was the major product detected. At E 11.5, POMC was processed to ACTH(1-39), des-acetyl alpha-MSH and beta-endorphin(1-31) and beta-endorphin(1-27). The amounts of these peptides increased at E 12.5, and at E 14.5. At E 14.5, there was a major increase in ACTH(1-39) and beta-endorphin(1-31) peptides. This was attributed to the large increase of corticotrophs in anterior pituitary at this stage. Des-acetyl alpha-MSH levels, however, were similar at E 12.5 and E 14.5 and the peptide was confined mainly to the central nervous system. gamma-MSH was not detected until E 16.5 in the brain. No alpha-MSH or acetylated beta-endorphin was detected between E 11.5 and E 14.5. Thus in early embryonic development, POMC is processed to des-acetyl alpha-MSH, beta-endorphin(1-31), beta-endorphin(1-27) and gamma-MSH in the brain, and primarily to ACTH(1-39) and beta-endorphin(1-31) in the anterior pituitary. Some differences exist in the forms of POMC-derived peptides found in embryonic versus adult brain and pituitary. The embryonic forms of the peptides may be significant in playing a role during development.