Ontogeny of acylated ghrelin degradation in the rat

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 μg AG intraperitoneally in rat neonates during the first 3 h of life. AG administration caused a 2–3 times increase in plasma AG concentrations contrasting with a ≈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.