Tropea Anna, Tiberi Federica, Minici Francesca, Orlando Mariateresa, Gangale Maria Francesca, Romani Federica, Miceli Fiorella, Catino Stefania, Mancuso Salvatore, Sanguinetti Maurizio, Lanzone Antonio, Apa Rosanna
Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy.
J Clin Endocrinol Metab. 2007 Aug;92(8):3239-45. doi: 10.1210/jc.2007-0180. Epub 2007 May 29.
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.
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.
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.
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.
The present in vitro study provides the first evidence of a direct inhibitory influence of ghrelin on human luteal function.
胃饥饿素是一种广为人知的食物摄入和能量平衡调节剂，是一种参与多种内分泌和非内分泌作用的相当普遍存在的肽。由于在人类黄体中已通过免疫组织化学检测到胃饥饿素及其受体（GRLN-R），因此有人提出胃饥饿素在调节黄体功能方面可能存在尚未明确的作用。
我们首先研究了黄体中期人黄体细胞中GRLN-R mRNA的表达。然后分析了胃饥饿素对基础状态和人绒毛膜促性腺激素（hCG）刺激的孕酮（P）释放的影响。最后，我们研究了胃饥饿素是否会影响黄体中血管内皮生长因子（VEGF）、前列腺素（PG）E2（两者均为促黄体生成因子）以及PGF2α（黄体溶解调节剂）的释放。分析了胃饥饿素对基础状态和缺氧刺激的黄体VEGF表达的影响。
将人黄体细胞与胃饥饿素（10^(-13)至10^(-7) m）、hCG（100 ng/ml）、CoCl2（10 microm，化学性缺氧）或hCG或CoCl2与胃饥饿素联合孵育24小时。通过实时RT-PCR评估GRLN-R mRNA和VEGF mRNA。通过放射免疫分析法测定PGs和P的释放，而通过酶联免疫吸附测定法测定VEGF的释放。
在人黄体细胞中证实了GRLN-R mRNA的表达。胃饥饿素显著降低了基础状态和hCG刺激的P释放，它能够减少PGE2并增加黄体PGF2α的释放。胃饥饿素显著降低了基础状态和缺氧刺激的VEGF释放，但不影响黄体VEGF mRNA的表达。
目前的体外研究首次提供了胃饥饿素对人黄体功能有直接抑制作用的证据。
