BIOSYNTHESIS AND PROCESSING OF PRO-OPIOMELANOCORTIN-DERIVED PEPTIDES DURING FETAL PITUITARY DEVELOPMENT

The MW forms of pro-opiomelanocortin (POMC)-derived peptides present in rat pituitaries during fetal and early postnatal development (embryonic day 14-3 day neonate) were investigated. At all early ages examined, the major immunoreactive form of ACTH was POMC. Only during late fetal and early postnatal stages did progressively larger amounts of 4.5K [kilodalton] ACTH, a major POMC processing end product, appear. This form was found almost exclusively in isolated anterior lobes. In contrast, 3.5K size endorphin(s), another POMC derivative, were present in whole glands even at early stages (day 14), and were the major POMC derivative(s) found in isolated intermediate-posterior lobes of older fetuses. Despite the early appearance of 3.5K endorphin(s), .alpha.-MSH did not appear until day 19 and was detected only in isolated intermediate-posterior lobes. Dispersed fetal pituitary cells were cultured in the presence of radioactive amino acids. After immunoprecipitation using affinity-purified antisera, followed by fractionation of the radiolabeled products, POMC biosynthesis does occur in cultures of day 14 embryonic pituitary cells, and that the major POMC-derived end product is 3.5K size endorphin(s). POMC is synthesized at least by day 14 of rat pituitary development and that lobe-specific processing characteristic of the corresponding adult lobe is apparent at the earliest stages that the lobes can be separated. The presence of 3.5K-sized endorphins at early ages is consistent with the possibility that POMC synthesis first occurs in the intermediate lobe. The noncoordinate appearance of .alpha.-MSH, 1-39 ACTH and endorphins implies that the activities of certain cleavage enzymes and acetylation enzymes responsible for lobe-specific post-translational POMC processing may be expressed at different times during development.