Sato S M, Mains R E
Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Ann N Y Acad Sci. 1987;512:286-99. doi: 10.1111/j.1749-6632.1987.tb24967.x.
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.
在促肾上腺皮质激素原/内啡肽加工的许多方面，新生黑素细胞在出生时就已成熟。新生黑素细胞能正确地将前体加工成许多预期产物，包括α-促黑素细胞激素（α-MSH）和β-内啡肽，黑素细胞会进行组织特异性修饰，如α-N-乙酰化和额外的蛋白水解步骤，并且它们对多巴胺能药物有反应，但对促肾上腺皮质激素释放因子（CRF）或糖皮质激素的生理水平无反应。这些特征在新生垂体中间叶细胞的无血清培养中得以保留。因此，垂体中间叶促黑素细胞的主要发育变化涉及从出生到成年促肾上腺皮质激素原/内啡肽合成速率净增加150倍。相比之下，新生垂体前叶中促肾上腺皮质激素原/内啡肽的加工在出生时并不成熟。在体内和体外，新生垂体前叶促肾上腺皮质激素细胞都含有大量的促肾上腺皮质激素原/内啡肽，并且大量的促肾上腺皮质激素（ACTH）（1-39）会裂解为促肾上腺皮质激素（1-13）NH2和促肾上腺皮质激素样中叶肽（CLIP）。令人惊讶的是，促肾上腺皮质激素（1-13）NH2和β-内啡肽的量随着培养时间的增加而增加，但在促肾上腺皮质激素细胞中未观察到促肾上腺皮质激素（1-13）NH2或β-内啡肽的α-N-乙酰化。与成年情况一样，新生促肾上腺皮质激素细胞中促肾上腺皮质激素原/内啡肽的合成受CRF和糖皮质激素的调节。此外，对新生促肾上腺皮质激素细胞进行糖皮质激素处理可抑制促肾上腺皮质激素（1-39）裂解为促肾上腺皮质激素（1-13）NH2以及β-促脂素裂解为β-内啡肽，使处理后的促肾上腺皮质激素细胞更类似于成年促肾上腺皮质激素细胞。在成年促肾上腺皮质激素细胞中未观察到新生促肾上腺皮质激素细胞中这种加工的可塑性。研究在此可塑性期间改变的肽加工模式是否会永久改变，以及这些改变的加工模式会有什么后果将很重要。
