Abstract OBJECTIVE: To study the relationship between Ghrelin and growth hormone secretagogue receptor (GHSR) expression and the catch-up growth in rats with intrauterine growth restriction (IUGR). METHODS: The rat model of IUGR was established by food restriction during pregnancy. The small for gestational age (SGA) and appropriate for gestational age (AGA) rat pups from the pregnant rats were used as the experimental group. The AGA rat pups from the pregnant rats without food restriction served as the control group. The samples from the stomach fundus and hypothalamus were taken postnatal days 0, 20 and 40. Ghrelin mRNA and GHSR mRNA expression were determined by real-time fluorescence quantitive PCR (real-time FQ-PCR). Ghrelin protein and GHSR protein expression were examined by immunohistochemistry (IHC). RESULTS: At postnatal day 0, both Gherlin mRNA and protein levels in the stomach fundus were significantly higher, while GHSR mRNA expression in the hypothalamus were significantly lower in SGA rats from food restriction group than those in AGA rats from restriction and control groups. At postnatal day 20, the ghrelin protein expression in the stomach of fundus, and GHSR mRNA and protein expression in the hypothalamus in SGA catch-up rats were significantly higher than those in SGA non-catch-up growth rats and AGA rats from the control group. At postnatal day 40, there were no significant differences among SGA catch-up growth rats, SGA non-catch-up growth rats and normal AGA rats. CONCLUSIONS: Ghrelin-GHSR might be involved in the physiological regulation and pathological process in IUGR rats. It is also possibly involved in the regulation of catch-up growth in the early life of SGA rats.［Chin J Contemp Pediatr, 2010, 12 (7):563-568］
YANG Hui-Ming,MAO Meng,YANG Fan et al. Relationship between Ghrelin and growth hormone secretagogue receptor expression and catch-up growth in rats with intrauterine growth restriction[J]. 中国当代儿科杂志, 2010, 12(07): 563-568.
YANG Hui-Ming,MAO Meng,YANG Fan et al. Relationship between Ghrelin and growth hormone secretagogue receptor expression and catch-up growth in rats with intrauterine growth restriction[J]. CJCP, 2010, 12(07): 563-568.
［1］Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach［J］. Nature, 1999, 402(6762):656-660.
［2］Takahashi H, Kurose Y, Kobayashi S, Sugino T, Kojima M, Kangawa K, et al. Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep［J］. J Endocrinol, 2006,189(1): 67-75.
［3］Vestergaard ET, Hansen TK, Gormsen LC, Jakobsen P, Moller N, Christiansen JS, et al. Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects［J］. Am J Physiol Endocrinol Metab, 2007, 292(6):E1829-1836.
［4］Iqbal J, Kurose Y, Canny B , Clarke IJ. Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep［J］. Endocrinology, 2006, 147(1): 510-519.
［5］Zigman JM, Jones JE, Lee CE, Saper CB, Elmquist JK. Expression of ghrelin receptor mRNA in the rat and the mouse brain［J］. J Comp Neurol, 2006, 494(3):528-548.
［6］Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite［J］. J Clin Invest, 2006, 116(12):3229-3239.
［7］Drazen DL, Vahl TP, D′Alessio DA, Seeley RJ, Woods SC. Effects of a fixed meal pattern on ghrelin secretion:Evidence for a learned response independent of nutrient status［J］. Endocrinology, 2006, 147(1): 23-30.
［8］Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity［J］. J Clin Invest, 2005, 115(12):3564-3572.
［9］Wang X, Liang L, Du L. The effects of intrauterine undernutrition on pancreas ghrelin and insulin expression in neonate rats［J］. J Endocrinol, 2007, 194(1): 121-129.
［10］Vestergaard ET, Dall R, Lange KH, Kjaer M, Christiansen JS, Jorgensen JO. The ghrelin response to exercise before and after growth hormone administration［J］. J Clin Endocrinol Metab, 2007, 92(1): 297-303.
［11］Vickers MH, Hofman PL, Gluckman PD, Lobie PE, Cutfield WS. Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat［J］. Am J Physiol Endocrinol Metab, 2006, 291(6): E1212-E1219.
［12］Lagrou K, Vanderfaeillie J, Froidecoeur C, Thomas M, Massa G, Tenoutasse S, et al. Effect of 2 years of high-dose growth hormone therapy on cognitive and psychosocial development in short children born small for gestational age［J］. Eur J Endocrinol, 2007, 156(2):195-201.
［13］Chiesa C, Osborn JF, Haass C, Natale F, Spinelli M, Scapillati E,et al. Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry?［J］. Clin Chem, 2008, 54(3): 550-558.
［14］Gohlke BC, Huber A, Hecher K, Fimmers R, Bartmann P, Roth CL. Fetal insulin-like growth factor (IGF)-I, IGF-II, and ghrelin in association with birth weight and postnatal growth in monozygotic twins with discordant growth［J］. J Clin Endocrinol Metab, 2005, 90(4): 2270-2274.
［15］Lee HM, Wang G, Englander EW, Kojima M, Greeley GeorgeH Jr. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations［J］. Endocrinology, 2002, 143（1）:185-190.
