The synthesis and processing of pro-ACTH/endorphin in the developing rat pituitary.
In many aspects of pro-ACTH/endorphin processing, newborn melanocytes are mature by birth. The newborn melanocytes correctly process precursor to many of the expected products including alpha MSH and beta-endorphin, the melanocytes perform tissue-specific modifications such as alpha-N-acetylation and additional proteolytic steps and they respond to dopaminergic agents but not to physiological levels of CRF or glucocorticoids. These features are retained in serum-free cultures of newborn intermediate pituitary cells. Thus, the major developmental alterations in the intermediate pituitary melanotropes involve the net 150-fold rise in pro-ACTH/endorphin synthetic rate, from birth to adulthood. In contrast, processing of pro-ACTH/endorphin in the newborn anterior lobe is not mature by birth. Both in vivo and in vitro newborn anterior pituitary corticotropes contain a large pool of pro-ACTH/endorphin, and a substantial amount of ACTH(1-39) is cleaved to ACTH(1-13)NH2 and CLIP. Surprisingly, the amount of ACTH(1-13)NH2 and beta-endorphin rises with increasing time in culture, but alpha-N-acetylation of ACTH(1-13)NH2 or beta-endorphin is not seen in the corticotropes. As in the adult, the synthesis of pro-ACTH/endorphin in newborn corticotropes is subject to regulation by CRF and glucocorticoids. In addition, glucocorticoid treatment of newborn corticotropes acts to suppress the cleavage of ACTH(1-39) to ACTH(1-13)NH2 and of beta-LPH to beta-endorphin, rendering the treated corticotropes more like the adult corticotropes. This plasticity in processing observed in the newborn corticotropes is not seen in the adult. It will be important to examine whether peptide processing patterns which are changed during this period of plasticity are permanently altered, and then what the consequences of those altered processing patterns might be.
Sato
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SM
Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Mains
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D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D010902:Pituitary Gland / Q000254:growth & development* / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000254:growth & development / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats
D011333:Pro-Opiomelanocortin