The determination of Ghrelin immunoreactivity in gastric mucosa of fundus during pregnancy in mice

Emrah Sur, Yasemin Oznurlu, Tugba Ozaydın


Ghrelin, called as appetite or hunger hormone, is mainly produced by gastric glands, and it stimulates appetite. Because of increasing food intake during pregnancy due to augmented metabolic demands, the gastrointestinal tract problems have more serious clinical importance in this period. The aim of this study was to determine the effects of pregnancy on ghrelin immunoreactivity in the gastric mucosa of fundus in mice. For this purpose a total of 20 Swiss albino female mice at 12–14 weeks of age were used. The tissue samples were collected on days 3 (early-E), 10 (mid-M), and 17 (late-L) of pregnancy. Tissue samples were taken from the great curvature of stomach. Ghrelin was demonstrated immunohistochemically using peroxidase-labelled streptavidin biotin complex method. H-score was used for semi quantitatively analysis of ghrelin-positive cells. Although the ghrelin-immunoreactive cells were scattered throughout the fundic glands, it was observed that they mainly located at the lower portion of these glands. Immunoreactivity was diffuse pattern in the cell cytoplasm. The ghrelin positive cells increased during pregnancy compared to non-pregnant control animals while the mean H-score, reflects the number and intensity of immunoreactive cells, was found the most higher at early and mid- gestational periods (C: 321,50±8,35; E: 419,20±11,24; M: 423,50±15,12; L: 378,05±17,07, p<0,05). It was concluded that these findings obtained from this study may suggested a new explanation for the relation to between the pregnancy and gastrointestinal disturbances.


Ghrelin immunohistochemistry, fundic gland, H-score, pregnant mouse

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. Makino Y, Hosoda H, Shibata K, Makino I, Kojima M, Kangawa K, et al. Alteration of plasma ghrelin levels associated with the blood pressure in pregnancy. Hypertension 2002; 39:781-4.

. Gündoğan M, Demirkan NÇ, Koray T, Aybek H. Gastric histopathological findings and ghrelin expression in morbid obesity. Türk Patoloji Derg 2013; 29:19-26.

. Castorina S, Loreto C, Musumeci G, Luca T, Privitera G, De Geronimo V, et al. Immunohistochemistry evidence for gastric ghrelin cells hypertrophy in obese patients. Ital J Anat Embryol. 2014; 119(1), Suppl: 41.

. Nakahara K, Nakagawa M, Baba Y, Sato M, Toshinai K, Date Y, et al. Maternal ghrelin plays an important role in rat fetal development during pregnancy. Endocrinology 2006; 147:1333-42.

. Kojima, M, Kangawa, K. Ghrelin: Structure and Function. Physiol Rev. 2005; 85:495-522.

. Morshed G, Rashed L, Hafez M. Ghrelin gastric tissue expression and wall thickness in patients submitted to laparoscopic sleeve gastrectomy as the primary weight loss procedure. Egyp J Surg. 2015; 34:245-50.

. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal ınitiation in humans. Diabetes 2001; 50:1714-19.

. Özfiliz N, Tütüncü Ş, Erdost H. Immunohistochemical distribution of ghrelin positive cells in the abomasum of sheep. Ankara Üniv Vet Fak Derg. 2011; 58:61-4.

. Langer FB, Hoda MAR, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzl E, et al. Sleeve gastrectomy and gastric banding: Effects on plasma ghrelin levels. Obes Surg. 2005; 15:1024-29.

. Tham E, Liu J, Innis S, Thompson D, Gaylinn BD, Bogarin R, et al. Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase. Am J Physiol Endocrinol Metab. 2009; 296(5): E1093-1100.

. Szczepankiewicz D, Skrzypski M, Pruszynska-Oszmalek E, Zimmermann D, Andralojc K, Kaczmarek P, et al. Importance of ghrelin in hypothalamus – pituitary axis on growth hormone release during normal pregnancy in the rat. J Physiol Pharmacol. 2010; 61(4):443-9.

. Palik E, Baranyi E, Melczer Z, Audikovszky M, Szocs A, Winkler G, et al. Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance. Diabetes Res Clin Pract. 2007; 76(3):351-7.

. Howat WJ, Wilson BA. Tissue fixation and the effect of molecular fixatives on downstream staining procedures. Methods 2014; 70:12-9.

. Paavilainen L, Edvinsson A, Asplund A, Hober S, Kamph C, Ponten F, et al. The impact of tissue fixatives on morphology and antibody-based protein profiling in tissues and cells. J Histochem Cytochem. 2010; 58:237-46.

. Godbole GB, Modi DN, Puri CP. Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli. Reproduction 2007;


. Sɫupecka M, Romanowicz K, Woliǹski J. Maternal high-fat diet during pregnancy and lactation influences obestatin and ghrelin concentrations in milk and plasma of Wistar rat dams and their offspring. Int J Endocrin, 2016; ID5739763.

. Rindi G, Necchi V, Torsello ASA, Zoli M, Raimondo VLF, Cocchi D, et al. Characterisation of gastric ghrelin cells in man and other mammals: studies in adult and fetal tissues. Histochem Cell Biol. 2002; 117:511-9.

. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000; 141:4255-61.

. Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun, 2001; 280:904-7.

. Sakata I, Sakai T. Ghrelin cells in the gastrointestinal tract. Int J Pept. 2010; ID 945056:doi:10.1155/2010/945056.

. Penkova N, Atanassova P. Immunohistochemical expression of ghrelin receptor GHS-R1 in the gastrointestinal tract. Acta Morphol. Anthropol. 2015; 22:42-5.

. Bossenmeyer-Pourie´ C, Blaise S, Pourie´ G, Tomasetto C, Audonnet S, Ortiou S, et al. Methyl donor deficiency affects fetal programming of gastric ghrelin cell organization and function in the rat. Am. J. Pathol. 2010; 176(1):270-7.

. Erdmann J, Lippl F, Schusdziarra V. Differential effect of protein and fat on plasma ghrelin levels in man. Regul. Pept. 2003; 116:101-7.

. Gao H, Tanchico DT, Yallampalli U, Balakrishnan MP, Yallampalli C. Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet. Physiol. Rep. 2015; 3(4):e12368.

. Fuglsang J, Skjærbæk C, Espelund U, Frystyk J, Fisker S, Flyvbjerg A, et al. Ghrelin and its relationship to growth hormones during normal pregnancy. Clin. Endocrinol. 2005; 62:554-9.

. Shibata K, Hosoda H, Kojima M, Kangawa K, Makinod Y, Makinod I, Kawarabayashi T, Futagami K, Gomita Y. Regulation of ghrelin secretion during pregnancy and lactation in the rat: possible involvement of hypothalamus. Peptide. 2004; 25:279-87.

. Ladyman SR, Augustine RA, Grattan DR. Hormone interactions regulating energy balance during pregnancy. J. Neuroendocrinol. 2010; 22:805-17.

. Osawa H, Nakazato M, Date Y, Kita H, Ohnishi H, Ueno H, et al. Gastritis associated with Helicobacter pylori. J Clin Endocrinol Metab. 2005; 90(1):10-6.



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