Advances in Clinical and Experimental Medicine
2014, vol. 23, nr 3, May-June, p. 363–370
Publication type: original article
Language: English
The Effects of Ovariectomy on Ghrelin Expression in the Rat Uterus
1 Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
Abstract
Background. Ghrelin is a hormone which has effects on the secretion of growth hormone, the gastrointestinal system, the cardiovascular system, cell proliferation and the reproductive system.
Objectives. The aim of this study is to investigate structural changes in the uterine tissue and to assess ghrelin immunoreactivity in the endometrium as a result of bilateral ovariectomization of rats.
Material and Methods. In this study, 28 adult female albino Wistar rats were used. The rats were randomly divided into four groups. Group I was the control group; Group II was the placebo group; Group III was ovariectomized; and Group IV was ovariectomized with 2mg/kg estrogen administered per day. Age-matched diestrous intact rats were used as controls. At the end of the experiment, the rats were decapitated 1, 3, 5, 7, and 15 days after ovariectomy under ketamine anesthesia and their uterine tissue was removed.
Results. In the ovariectomized rats, reductions in the sizes of both the uterine epithelium and the endometrial glands were observed, as well as a loss of connective tissue. Ghrelin-positive cells in the endometrial surface and the gland epithelium were visualized by immunohistochemistry. After ovariectomization, ghrelin expression was found to be decreased in a time dependent manner.
Conclusion. Bilateral ovariectomization leads to histological changes in the uterine tissue. Ovariectomization was observed to decrease endometrium ghrelin immunoreactivity.
Key words
endometrium, ghrelin, immunoreactivity, ovariectomy, rats.
References (35)
- Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999, 402, 656–660.
- Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 2001, 409, 194–198.
- Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K: Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 2000, 486, 213–216.
- Sonmez MF, Ozan E: Determination of ghrelin immunoreactivity in the rat stomach after fasting and refeeding. Acta Histochem 2007, 109, 193–199.
- Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, Yoshida T, Kojima M, Kangawa K, Toyoda N: Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 2003, 88, 2335–2340.
- Arvat E, Maccario M, Di Vito L, Broglio F, Benso A, Gottero C, Papotti M, Muccioli G, Dieguez C, Casanueva FF, Deghenghi R, Camanni F, Ghigo E: Endocrine activities of ghrelin, a natural growth hormone secretagogue (ghs), in humans: Comparison and interactions with hexarelin, a nonnatural peptidyl ghs, and gh-releasing hormone. J Clin Endocrinol Metab 2001, 86, 1169–1174.
- Tschop M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 2000, 407, 908–913.
- Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR: The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000, 141, 4325–4328.
- Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB: Ghrelin – a hormone with multiple functions. Front Neuroendocrinol 2004, 25, 27–68.
- Broglio F, Arvat E, Benso A, Papotti M, Muccioli G, Deghenghi R, Ghigo E: Ghrelin: Endocrine and nonendocrine actions. J Pediatr Endocrinol Metab 2002, 15, 1219–1227.
- Jeffery PL, Herington AC, Chopin LK: The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Cytokine Growth Factor Rev 2003, 14, 113–122.
- Barreiro ML, Tena-Sempere M: Ghrelin and reproduction: A novel signal linking energy status and fertility? Mol Cell Endocrinol 2004, 226, 1–9.
- Tena-Sempere M: Ghrelin: Novel regulator of gonadal function. J Endocrinol Invest 2005, 28, 26–29.
- Fernandez-Fernandez R, Tena-Sempere M, Aguilar E, Pinilla L: Ghrelin effects on gonadotropin secretion in male and female rats. Neurosci Lett 2004, 362, 103–107.
- Lorenzi T, Meli R, Marzioni D, Morroni M, Baragli A, Castellucci M, Gualillo O, Muccioli G: Ghrelin: A metabolic signal affecting the reproductive system. Cytokine Growth Factor Rev 2009, 20, 137–152.
- Furuta M, Funabashi T, Kimura F: Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats. Biochem Biophys Res Commun 2001, 288, 780–785.
- Vulliemoz NR, Xiao E, Xia-Zhang L, Germond M, Rivier J, Ferin M: Decrease in luteinizing hormone pulse frequency during a five-hour peripheral ghrelin infusion in the ovariectomized rhesus monkey. J Clin Endocrinol Metab 2004, 89, 5718–5723.
- 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. Endocrinology 2006, 147, 510–519.
- Lasota A, Danowska-Klonowska D: Experimental osteoporosis – different methods of ovariectomy in female white rats. Rocz Akad Med Bialymst 2004, 49, 129–131.
- Sonmez MF, Narin F, Balcioglu E: Melatonin and Vitamin C Attenuates Alcohol-Induced Oxidative Stress in Aorta. Basic Clin Pharmacol Toxicol 2009, 105, 410–415.
- Hawkins NJ, Ward RL: Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst 2001, 93, 1307–1313.
- Yang XH, Wu QL, Yu XB, Xu CX, Ma BF, Zhang XM, Li SN, Lahn BT, Xiang AP: Nestin expression in different tumours and its relevance to malignant grade. J Clin Pathol 2008, 61, 467–473.
- Hayashida T, Murakami K, Mogi K, Nishihara M, Nakazato M, Mondal MS, Horii Y, Kojima M, Kangawa K, Murakami N: Ghrelin in domestic animals: Distribution in stomach and its possible role. Domest Anim Endocrinol 2001, 21, 17–24.
- Hardy K, Spanos S: Growth factor expression and function in the human and mouse preimplantation embryo. J Endocrinol 2002, 172, 221–236.
- Gualillo O, Caminos JE, Nogueiras R, Seoane LM, Arvat E, Ghigo E, Casanueva FF, Dieguez C: Effect of food restriction on ghrelin in normal-cycling female rats and in pregnancy. Obes Res 2002, 10, 682–687.
- Kawamura K, Sato N, Fukuda J, Kodama H, Kumagai J, Tanikawa H, Nakamura A, Honda Y, Sato T, Tanaka T: Ghrelin inhibits the development of mouse preimplantation embryos in vitro. Endocrinology 2003, 144, 2623–2633.
- Aghajanova L, Rumman A, Altmäe S, Wånggren K, Stavreus-Evers A: Diminished endometrial expression of ghrelin and ghrelin receptor contributes to infertility. Reprod Sci 2010, Sep 17, 823–832.
- Fernandez-Fernandez R, Navarro VM, Barreiro ML, Vigo EM, Tovar S, Sirotkin AV, Casanueva FF, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M: Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat. Endocrinology 2005, 146, 3018–3025.
- Caminos JE, Tena-Sempere M, Gaytan F, Sanchez-Criado JE, Barreiro ML, Nogueiras R, Casanueva FF, Aguilar E, Dieguez C: Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology 2003, 144, 1594–1602.
- Gaytan F, Barreiro ML, Chopin LK, Herington AC, Morales C, Pinilla L, Casanueva FF, Aguilar E, Dieguez C, Tena-Sempere M: Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary. J Clin Endocrinol Metab 2003, 88, 879–887.
- Viani I, Vottero A, Tassi F, Cremonini G, Sartori C, Bernasconi S, Ferrari B, Ghizzoni L: Ghrelin inhibits steroid biosynthesis by cultured granulosa-lutein cells. J Clin Endocrinol Metab 2008, 93, 1476–1481.
- Murray MK: The effect of estrogen and progesterone on structural changes in the uterine glandular epithelium of the ovariectomized sheep. Biol Reprod 1992, 47, 408–417.
- Gualillo O, Caminos JE, Kojima M, Kangawa K, Arvat E, Ghigo E, Casanueva FF, Dieguez C: Gender and gonadal influences on ghrelin mrna levels in rat stomach. Eur J Endocrinol 2001, 144, 687–690.
- Matsubara M, Sakata I, Wada R, Yamazaki M, Inoue K, Sakai T: Estrogen modulates ghrelin expression in the female rat stomach. Peptides 2004, 25, 289–297.
- Zhang Y, Na X, Li L, Zhao X, Cui H: Isoflavone reduces body weight by decreasing food intake in ovariectomized rats. Ann Nutr Metab 2009, 54, 163–170.


