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Submitted on August 3, 2004
Accepted on November 23, 2004
Departments of Cell Biology, Physiology and Immunology (F.G., M.L.B., E.A., M.T.-S.), and Pathology (C.M.), University of Córdoba, 14004 Córdoba, Spain; Departments of Physiology (C.D.) and Medicine (F.F.C.), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain; and School of Life Sciences, Cluster for Molecular Biotechnology (P.J., L.K.C., A.C.H.), Queensland University of Technology, Brisbane, Queensland, Australia
* To whom correspondence should be addressed. E-mail: fi1tesem{at}uco.es.
Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is a newly identified, ubiquitously expressed molecule which has been involved in a wide array of endocrine and non-endocrine functions, including cell proliferation. In this context, our group has recently reported the expression of ghrelin and its functional receptor, the GHS-R type 1a, in the human ovary and testis, as well as in several testicular tumors. Ovarian malignancies, however, remain unexplored. Notably, a vast majority of ovarian tumors derive from the surface epithelium, which originates from the celomic epithelium. Considering the proven expression of ghrelin in the human ovary, and its reported effects in the proliferative activity of different cancer cell lines, we aimed at evaluating whether the ovarian surface epithelium, as well as related reproductive structures and tumors, are potential targets of ghrelin. To this end, expression of GHS-R1a was analyzed by immuno-histochemistry in a panel of normal, metaplastic and neoplastic tissues. Uniform GHS-R1a immunostaining was detected throughout the ovarian surface epithelium. Likewise, ciliated cells within the Fallopian tube epithelium showed strong GHS-R1a expression. In contrast, other celomic derivatives, such as endometrium and endocervix, were negative for GHS-R1a immunoreactivity. In keeping with data from normal tissues, inclusion cysts from the surface epithelium expressed GHS-R1a. Similarly, benign serous tumors resembling Fallopian tube epithelium were also positive, whereas serous cystadenocarcinomas showed GHS-R1a expression only in highly differentiated specimens. In contrast, other neoplasms, such as mucinous cystadenomas and cystadenocarcinomas, endometrioid tumors, clear cell carcinomas and Brenner tumors, did not express GHS-R1a. In conclusion, our results demonstrate that the ovarian surface epithelium and related tumors are potential targets for systemic or locally produced ghrelin, as they express the functional type 1a GHS-R. Considering the relevant role of the ovarian surface epithelium in key physiological events (such as ovulation) and neoplastic transformation of the ovary, the potential actions of ghrelin in those phenomena merit further investigation.
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