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This version published online on May 29, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0180
A more recent version of this article appeared on August 1, 2007
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Submitted on January 24, 2007
Accepted on May 23, 2007

Ghrelin affects the release of luteolytic and luteotropic factors in human luteal cells

Anna Tropea, Federica Tiberi, Francesca Minici, Mariateresa Orlando, Maria Francesca Gangale, Federica Romani, Fiorella Miceli, Stefania Catino, Salvatore Mancuso, Maurizio Sanguinetti, Antonio Lanzone, and Rosanna Apa*

Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore (UCSC), 00168 Roma, Italy; Istituto Scientifico Internazionale "Paolo VI", UCSC, 00168 Roma, Italy; Istituto di Ricerca "Associazione OASI Maria SS ONLUS", 94018 Troina (EN), Italy; Instituto di Microbiologia, UCSC, 00168 Roma, Italy

* To whom correspondence should be addressed. E-mail: krimisa{at}libero.it.

Context: Ghrelin, well-known modulator of food intake and energy balance, is a rather ubiquitous peptide involved in several endocrine and non-endocrine actions. A possible as-yet-unknown role for ghrelin in modulating luteal function has been suggested, as both ghrelin and its receptor (GRLN-R) have been immunohistochemically detected in human corpus luteum.

Objective: We first investigate GRLN-R mRNA expression in mid-luteal phase human luteal cells. Ghrelin effect on basal and hCG-stimulated progesterone (P) release was then analyzed. Finally, we investigated whether ghrelin could affect luteal release of vascular endothelial growth factor (VEGF), prostaglandin (PG) E2 (PGE2) -both luteotropic factors- and PGF2{alpha} -luteolytic modulator. Ghrelin effect on both basal and hypoxia-stimulated VEGF luteal expression was analyzed.

Methods: Human luteal cells were incubated for 24h with ghrelin (10-13-10-7 M) or hCG (100 ng/ml) or CoCl2 (10 µM) -chemical hypoxia- or with hCG or CoCl2 in combination with ghrelin. Both GRLN-R mRNA and VEGF mRNA were evaluated by real-time RT-PCR. PGs and P release was assayed by RIA, while VEGF release by ELISA.

Results: GRLN-R mRNA expression was demonstrated in human luteal cells. Both basal and hCG-stimulated P release was significantly decreased by ghrelin, that was able to reduce PGE2 and increase PGF2{alpha} luteal release. Both basal and hypoxia-stimulated VEGF release was significantly decreased by ghrelin, that did not affect VEGF mRNA luteal expression.

Conclusions: The present in vitro study provides the first evidence of a direct inhibitory influence of ghrelin on human luteal function.
Key words: Ghrelin • human luteal cells • GRLN-R • Progesterone • Prostanoids • VEGF






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