Ontogenesis of proopiomelanocortin and its processing to beta-endorphin by the fetal and neonatal rat brain.

A number of reports suggest that beta-endorphin (beta-END) may play an important role in the regulation of cell proliferation and neuronal differentiation. Proopiomelanocortin (POMC), the common precursor ofadrenocorticotropic hormone and beta-END, is detected very early in embryonic life in hypothalamic neurons of the developing rat. However, very little is known about the degree to which POMC is processed to beta-END during fetal and early postnatal life. Thus, it was the objective of the present study to estimate the hypothalamic content of POMC mRNA, as well as the biosynthesis and posttranslational processing of POMC by hypothalamic neurons on fetal day 20 and on days 1, 8 and 22 of postnatal life. Hypothalamic POMC mRNA, as determined by Northern blot analysis, was higher on fetal day 20 than on postnatal days 1, 8 and 22. A higher rate of incorporation of [(3)H]phenylalanine into beta-END immunoreactive peptides was observed on fetal day 20 than on postnatal day 1. However, the rate of incorporation was significantly increased by day 8 of postnatal life and was similar to that on day 22. POMC was processed to beta-lipotropin (beta-LPH) and beta-END at all ages examined, but the relative proportions of POMC:beta-LPH:beta-END changed during development. Thus, beta-END accounted only for 34.89 +/- 6.14% of the total [(3)H]phenylalanine-labeled beta-END immunoreactive peptides on fetal day 20, while it accounted for 57. 37 +/- 5.20, 62.81 +/- 1.38 and 79.25 +/- 6.57% on days 1, 8 and 22 of postnatal life, respectively. Thus, POMC is processed to a considerable extent into beta-END-sized peptides by the fetal hypothalamus and may influence brain development. Furthermore, the rate of processing of hypothalamic POMC into beta-END increases with development, probably due to the increased activity of the enzymes specific for POMC processing. Copyright 2000 S. Karger AG, Basel