Ghrelin affects the release of luteolytic and luteotropic factors in human luteal cells.
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.
Tropea
Anna
A
Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy.
Tiberi
Federica
F
Minici
Francesca
F
Orlando
Mariateresa
M
Gangale
Maria Francesca
MF
Romani
Federica
F
Miceli
Fiorella
F
Catino
Stefania
S
Mancuso
Salvatore
S
Sanguinetti
Maurizio
M
Lanzone
Antonio
A
Apa
Rosanna
R
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
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