Bresciani E, Pitsikas N, Tamiazzo L, Luoni M, Bulgarelli I, Cocchi D, Locatelli V, Torsello A
Department of Experimental Medicine, University of Milano-Bicocca, 20052 Monza, Italy.
J Endocrinol Invest. 2008 Jul;31(7):647-52. doi: 10.1007/BF03345618.
Ghrelin, a 28-amino-acid peptide isolated from the stomach, is the natural ligand of the GH-secretagogues receptor-1a (GHS-R1a) and, so far, the only discovered circulating appetite-stimulating hormone. Similarly to ghrelin, many synthetic compounds belonging to the GHS family stimulate both GH secretion and feeding, whereas some stimulate GH secretion only. In the past years, studies have focused on the potential of the GHS to stimulate GH release during long-term treatment in humans and experimental animals. Few data are available about the extraendocrine effects of the GHS during several weeks of treatment, particularly in old rats. The aim of the present study was first to identify the lowest dose of hexarelin giving maximal stimulation of food intake both in young (3-month-old) and old rats (24-month-old). A dose-response study (80-320 microg/kg, s.c.) revealed that hexarelin at the dose of 80 microg/kg gave reproducibly maximal stimulation of food consumption in young as well as in old rats. Second, we evaluated the effect of 8-week daily sc treatment with hexarelin in young and old male rats. The outcome of the chronic study was that hexarelin (80 microg/kg, s.c., once daily) maintained a persistent significant orexigenic action throughout the treatment period, both in young and old rats. Interestingly, hexarelin treatment did not affect body weight gain either in young or old rats. We conclude that hexarelin is endowed with long-lasting orexigenic activity and might represent a potential therapeutic approach for pathological conditions characterized by a decline in food intake.
胃饥饿素是一种从胃中分离出的由28个氨基酸组成的肽，是生长激素促分泌素受体-1a（GHS-R1a）的天然配体，也是迄今为止唯一发现的循环中刺激食欲的激素。与胃饥饿素类似，许多属于GHS家族的合成化合物既能刺激生长激素分泌又能刺激进食，而有些则仅刺激生长激素分泌。在过去几年中，研究聚焦于GHS在人类和实验动物长期治疗期间刺激生长激素释放的潜力。关于GHS在数周治疗期间的内分泌外作用的数据很少，尤其是在老年大鼠中。本研究的目的首先是确定在年轻（3个月大）和老年大鼠（24个月大）中能最大程度刺激食物摄入量的六肽生长激素释放肽的最低剂量。一项剂量反应研究（80 - 320微克/千克，皮下注射）表明，80微克/千克剂量的六肽生长激素释放肽能在年轻和老年大鼠中均可重复地最大程度刺激食物消耗。其次，我们评估了在年轻和老年雄性大鼠中每日皮下注射六肽生长激素释放肽8周的效果。慢性研究的结果是，六肽生长激素释放肽（80微克/千克，皮下注射，每日一次）在整个治疗期间在年轻和老年大鼠中均维持持续显著的促食欲作用。有趣的是，六肽生长激素释放肽治疗对年轻或老年大鼠的体重增加均无影响。我们得出结论，六肽生长激素释放肽具有持久的促食欲活性，可能代表一种针对以食物摄入量下降为特征的病理状况的潜在治疗方法。
