Endocrinology and Diabetes Unit, British Columbia Children's Hospital, University of British Columbia, Vancouver V6H 3V4, Canada.
Peptides. 2010 Feb;31(2):301-6. doi: 10.1016/j.peptides.2009.11.016. Epub 2009 Nov 26.
Ghrelin circulates as acylated (AG) and unacylated (or desacyl) ghrelin (UAG). We aimed at clarifying the effect of age and sex on plasma deacylation and degradation of AG in vivo and in vitro in the rat. In vivo, we compared AG and UAG concentrations following administration of 1 microg AG intraperitoneally in rat neonates during the first 3h of life. AG administration caused a 2-3 times increase in plasma AG concentrations contrasting with a approximately 1000 times increase in UAG concentrations suggesting rapid deacylation of AG into UAG. In vitro, we demonstrated that AG degradation was greater in the fetus (97% over 30 min) and decreased progressively to 57% in adult animals (P<0.001). Carboxylesterase and butyrylcholinesterase activities were determined during the fetal (day 21 of pregnancy) and postnatal period (days 1, 6, 13, 21 and 28) and in the adult rat and were found to increase with age (P<0.001). While inhibition of carboxylesterase and butyrylcholinesterase did not affect AG deacylation, serine protease inhibitors decreased AG degradation in the adult rat (from 59% to 23%) and, to a lesser extent, in the rat neonate (from 92% to 57%) by reducing both deacylation and degradation into non-UAG metabolites. Our data suggest that degradation of AG into UAG and non-UAG metabolites is much faster in the fetus and in the rat neonate compared to the adult. We speculate that this process allows for fine tuning of the physiological effects of both AG and UAG.
生长激素释放肽（Ghrelin）以酰化（AG）和非酰化（或去酰化）形式（UAG）循环。我们旨在阐明年龄和性别对体内和体外大鼠 AG 去酰化和降解的影响。在体内，我们比较了新生大鼠生命的头 3 小时内腹膜内给予 1 微克 AG 后 AG 和 UAG 的浓度。AG 给药导致血浆 AG 浓度增加 2-3 倍，而 UAG 浓度增加约 1000 倍，表明 AG 快速去酰化为 UAG。在体外，我们证明 AG 降解在胎儿中更大（30 分钟内 97%），并随著年龄的增长逐渐降低至成年动物的 57%（P<0.001）。在胎儿（妊娠第 21 天）和产后（第 1、6、13、21 和 28 天）和成年大鼠期间测定了羧基酯酶和丁酰胆碱酯酶的活性，发现它们随著年龄的增长而增加（P<0.001）。虽然羧基酯酶和丁酰胆碱酯酶的抑制不影响 AG 的去酰化，但丝氨酸蛋白酶抑制剂降低了成年大鼠（从 59%降至 23%）和新生大鼠（从 92%降至 57%）中 AG 的降解，通过减少去酰化和降解为非 UAG 代谢物。我们的数据表明，与成年大鼠相比，胎儿和新生大鼠中 AG 降解为 UAG 和非 UAG 代谢物的速度要快得多。我们推测，这个过程允许精细调节 AG 和 UAG 的生理效应。
