title: Ghrelin affects the release of luteolytic and luteotropic factors in human luteal cells.
abstract: BACKGROUND
  Ghrelin, well-known modulator of food intake and energy balance, is a rather ubiquitous peptide involved in several endocrine and nonendocrine actions. A possible as-yet-unknown role for ghrelin in modulating luteal function has been suggested because both ghrelin and its receptor (GRLN-R) have been immunohistochemically detected in human corpus luteum.
  
  
  OBJECTIVE
  We first investigated GRLN-R mRNA expression in midluteal phase human luteal cells. Ghrelin effect on basal and human chorionic gonadotropin (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) E(2), both luteotropic factors, and PGF(2alpha), luteolytic modulator. Ghrelin effect on both basal and hypoxia-stimulated VEGF luteal expression was analyzed.
  
  
  METHODS
  Human luteal cells were incubated for 24 h with ghrelin (10(-13) to 10(-7) m) or hCG (100 ng/ml) or CoCl(2) (10 microm), chemical hypoxia, or with hCG or CoCl(2) 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, whereas 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, which was able to reduce PGE(2) and increase PGF(2alpha) luteal release. Both basal and hypoxia-stimulated VEGF release was significantly decreased by ghrelin, which 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.
authors.affiliation: Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tropea
authors.forename: Federica
authors.initials: F
authors.lastname: Tiberi
authors.forename: Francesca
authors.initials: F
authors.lastname: Minici
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Orlando
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Gangale
authors.forename: Federica
authors.initials: F
authors.lastname: Romani
authors.forename: Fiorella
authors.initials: F
authors.lastname: Miceli
authors.forename: Stefania
authors.initials: S
authors.lastname: Catino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mancuso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzone
authors.forename: Rosanna
authors.initials: R
authors.lastname: Apa
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D017931:DNA Primers; D003627:Data Interpretation, Statistical; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes; D054439:Ghrelin; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D003341:Luteolysis / Q000502:physiology*; D036361:Peptide Hormones / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D054440:Receptors, Ghrelin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D017931:DNA Primers; D005456:Fluorescent Dyes; D054439:Ghrelin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D015237:Dinoprost; C018021:cobaltous chloride; D015232:Dinoprostone