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Departments of Physiology (J.E.C., R.N., C.D.) and Medicine, Molecular Endocrinology Section (F.F.C.), University of Santiago de Compostela School of Medicine, 15705 Santiago de Compostela, Spain; and Department of Cell Biology, Physiology, and Immunology (M.T.-S., F.G., J.E.S.-C., M.L.B., E.A.), University of Córdoba, 14004 Córdoba, Spain
Address all correspondence and requests for reprints to: Prof. Carlos Diéguez, Department of Physiology, University of Santiago de Compostela School of Medicine, C/S. Francisco 1, 15705 Santiago de Compostela, Spain. E-mail: fscadigo{at}usc.es.
Ghrelin, a 28-amino acid acylated peptide, has been recently identified as the endogenous ligand for the GH secretagogue receptor. Previous studies demonstrated that ghrelin, acting centrally, strongly stimulates GH release and food intake. In this study we provide novel evidence for the expression of ghrelin in the cyclic and pregnant rat ovary. Persistent expression of ghrelin gene was demonstrated in rat ovary throughout the estrous cycle, although its relative mRNA levels varied depending on the stage of the cycle, with the lowest levels in proestrus and peak expression values on diestrous d 1, i.e. during the luteal phase of the cycle. Ghrelin immunoreactivity was predominantly located in the luteal compartment of the ovary; with intense immunostaining being detected in steroidogenic cells from corpus luteum of the current cycle as well as in all generations of regressing corpora lutea. Indeed, predominant expression of ghrelin in the corpus luteum was confirmed using a pseudopregnant rat model, where maximum ghrelin mRNA levels were detected in dissected luteal tissue. To note, the cyclicity in the profile of ovarian expression of ghrelin appeared to be tissue specific, as it was not detected in the stomach, nor was it observed in terms of circulating ghrelin levels. In addition, cyclic expression of ovarian ghrelin mRNA was disrupted by blockade of the preovulatory gonadotropin surge and ovulation by means of administration of a potent GnRH antagonist. Finally, ghrelin mRNA expression was persistently detected in rat ovary throughout pregnancy, with higher levels in early pregnancy and lower expression during the later part of gestation. In conclusion, our data provide novel evidence for the expression of ghrelin in the cyclic and pregnant rat ovary. Dynamic changes in the profile of ghrelin expression were detected during the estrous cycle and throughout pregnancy, thus suggesting a precise regulation of ovarian expression of ghrelin. Overall, our present findings may represent an additional link between body weight homeostasis and female reproductive function.
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