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Biosynthesis and processing of pro-opiomelanocortin-derived peptides during fetal pituitary development
Insights
Pro-opiomelanocortin (POMC) is synthesized by Day 14 in developing rat pituitaries. Lobe-specific processing of POMC peptides, like endorphins and ACTH, begins early, with distinct enzyme activities emerging over time.
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Endocrinology
Background:
- Pro-opiomelanocortin (POMC) is a precursor protein for various peptide hormones.
- Understanding POMC processing during development is crucial for comprehending pituitary function.
Purpose of the Study:
- To investigate the molecular weight forms of POMC-derived peptides during rat pituitary development.
- To determine the onset of POMC synthesis and lobe-specific processing.
Main Methods:
- Analysis of POMC peptide forms in rat pituitaries from embryonic Day 14 to postnatal Day 3.
- Culture of dispersed fetal pituitary cells with radioactive amino acids.
- Immunoprecipitation and fractionation of radiolabeled POMC products.
Main Results:
- POMC was the major immunoreactive corticotropin (ACTH) form at early developmental stages.
- 3.5K endorphins were present from Day 14, while alpha-melanocyte-stimulating hormone (α-MSH) appeared later.
- Lobe-specific processing patterns, characteristic of adult lobes, were observed early.
- POMC biosynthesis was confirmed in Day 14 embryonic pituitary cells, producing 3.5K endorphins.
Conclusions:
- POMC synthesis begins by Day 14 of rat pituitary development.
- Lobe-specific POMC processing is evident early in development.
- The differential timing of peptide appearance suggests distinct developmental regulation of processing enzymes.
Abstract:
We have investigated the molecular weight forms of pro-opiomelanocortin (POMC)-derived peptides present in rat pituitaries during fetal and early postnatal development (embryonic Day 14 to 3 day neonate). At all early ages examined, the major immunoreactive form of corticotropin (ACTH) was POMC. Only during late fetal and early postnatal stages did progressively larger amounts of 4.5K 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. We have also cultured dispersed fetal pituitary cells in the presence of radioactive amino acids. After immunoprecipitation using affinity-purified antisera, followed by fractionation of the radiolabeled products, we found that POMC biosynthesis does occur in cultures of Day 14 embryonic pituitary cells, and that the major POMC-derived end product produced is 3.5K size endorphin(s). These findings demonstrate that 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.