胎儿猴垂体发育过程中阿片促黑激素原（POMC）衍生肽的翻译后加工。I.促肾上腺皮质激素（ACTH）和α-促黑素（α-MSHs）。

Post-translational processing of pro-opiomelanocortin (POMC)-derived peptides during fetal monkey pituitary development. I. Adrenocorticotropin (ACTH) and alpha-melanotropins (alpha-MSHs).

作者信息

Allen R G, Hatfield J M, Stack J

机构信息

Department of Biochemistry, Oregon Health Sciences University, Portland 97201.

出版信息

Dev Biol. 1988 Mar;126(1):156-63. doi: 10.1016/0012-1606(88)90249-7.

DOI:10.1016/0012-1606(88)90249-7

PMID:2830157

Abstract

We have studied the post-translational processing of POMC-derived peptides during fetal monkey development using immunoassay and reverse-phase high-performance liquid chromatography (RP HPLC). Pituitary tissues obtained from fetal monkeys ranging from Gestational Day 50 to 155 were fractionated and analyzed for ACTH- and alpha-MSH-related peptides and compared to adult forms. Extracts of whole pituitary from Fetal Days 50 and 55 contained ACTH(1-39) and very small amounts of CLIP (corticotropin-like intermediate-lobe peptide; ACTH(18-39))-like immunoactivity. Acetylated alpha-MSHs were not detectable at Day 50. alpha-MSHs were barely detectable at Day 55. By Day 65, when pituitary lobes were separable, small amounts of des-, mono-, and diacetyl alpha-MSH were detectable in NIL extracts, but not in anterior lobe extracts. ACTH(1-39) levels were negligible when compared to increasing alpha-MSHs through Fetal Day 80 to 155 in the intermediate lobe. The CLIP immunoactivity was negligible in Day 80 and adult anterior lobe extracts. Thus, lobe-specific proteolytic processing of ACTH-related peptides was well established by midterm gestation. Marked increases of alpha-N- and alpha-N,O-acetylated forms of alpha-MSHs were detected during middle and late stage fetal development. Diacetyl alpha-MSH was the predominant form of alpha-MSH in adult NIL extracts. No acetylated alpha-MSHs were found in anterior lobe tissues, thus adult anterior lobe extracts contained almost exclusively ACTH(1-39). However adult NIL extracts contained two distinct forms of CLIP-related immunoactivity. Therefore changes in post-translational processing patterns of ACTH-related and alpha-MSH-related peptides continued to some extent, postnatally. These data indicate that marked changes in post-translational processing of POMC-derived ACTH-related products occur during the first half of monkey gestation.

摘要

我们利用免疫测定法和反相高效液相色谱法（RP HPLC）研究了胎猴发育过程中源自阿黑皮素原（POMC）的肽段的翻译后加工过程。对妊娠第50天至155天的胎猴垂体组织进行分级分离，并分析促肾上腺皮质激素（ACTH）和α-促黑素（α-MSH）相关肽段，并与成年形式进行比较。妊娠第50天和55天的全垂体提取物中含有ACTH(1-39)和极少量的类促肾上腺皮质激素中间叶肽（CLIP；促肾上腺皮质激素(18-39)）样免疫活性。在第50天时未检测到乙酰化的α-MSH。在第55天时α-MSH几乎检测不到。到第65天时，垂体叶可分离，在中间叶提取物中可检测到少量的去乙酰化、单乙酰化和二乙酰化α-MSH，但在前叶提取物中未检测到。与中间叶中从胎龄80天到155天不断增加的α-MSH相比，ACTH(1-39)水平可忽略不计。在第80天和成年前叶提取物中，CLIP免疫活性可忽略不计。因此，在妊娠中期，ACTH相关肽段的叶特异性蛋白水解加工已充分确立。在胎儿发育的中期和后期，检测到α-MSH的α-N-和α-N,O-乙酰化形式显著增加。二乙酰化α-MSH是成年中间叶提取物中α-MSH的主要形式。在前叶组织中未发现乙酰化的α-MSH，因此成年前叶提取物几乎只含有ACTH(1-39)。然而，成年中间叶提取物含有两种不同形式的CLIP相关免疫活性。因此，ACTH相关和α-MSH相关肽段的翻译后加工模式的变化在出生后仍在一定程度上持续。这些数据表明，在猴妊娠的前半期，源自POMC的ACTH相关产物的翻译后加工发生了显著变化。