Caminos J E, Tena-Sempere M, Gaytán F, Sanchez-Criado J E, Barreiro M L, Nogueiras R, Casanueva F F, Aguilar E, Diéguez C
Department of Physiology, University of Santiago de Compostela School of Medicine, 15705 Santiago de Compostela, Spain.
Endocrinology. 2003 Apr;144(4):1594-602. doi: 10.1210/en.2002-221058.
Ghrelin, a 28-amino acid acylated peptide, has been recently identified as the endogenous ligand for the GH secretagogue receptor. Previous studies demonstrated that ghrelin, acting centrally, strongly stimulates GH release and food intake. In this study we provide novel evidence for the expression of ghrelin in the cyclic and pregnant rat ovary. Persistent expression of ghrelin gene was demonstrated in rat ovary throughout the estrous cycle, although its relative mRNA levels varied depending on the stage of the cycle, with the lowest levels in proestrus and peak expression values on diestrous d 1, i.e. during the luteal phase of the cycle. Ghrelin immunoreactivity was predominantly located in the luteal compartment of the ovary; with intense immunostaining being detected in steroidogenic cells from corpus luteum of the current cycle as well as in all generations of regressing corpora lutea. Indeed, predominant expression of ghrelin in the corpus luteum was confirmed using a pseudopregnant rat model, where maximum ghrelin mRNA levels were detected in dissected luteal tissue. To note, the cyclicity in the profile of ovarian expression of ghrelin appeared to be tissue specific, as it was not detected in the stomach, nor was it observed in terms of circulating ghrelin levels. In addition, cyclic expression of ovarian ghrelin mRNA was disrupted by blockade of the preovulatory gonadotropin surge and ovulation by means of administration of a potent GnRH antagonist. Finally, ghrelin mRNA expression was persistently detected in rat ovary throughout pregnancy, with higher levels in early pregnancy and lower expression during the later part of gestation. In conclusion, our data provide novel evidence for the expression of ghrelin in the cyclic and pregnant rat ovary. Dynamic changes in the profile of ghrelin expression were detected during the estrous cycle and throughout pregnancy, thus suggesting a precise regulation of ovarian expression of ghrelin. Overall, our present findings may represent an additional link between body weight homeostasis and female reproductive function.
胃饥饿素是一种由28个氨基酸组成的酰化肽，最近被确定为生长激素促分泌素受体的内源性配体。先前的研究表明，胃饥饿素通过中枢作用强烈刺激生长激素释放和食物摄入。在本研究中，我们提供了胃饥饿素在大鼠周期性和妊娠卵巢中表达的新证据。尽管胃饥饿素基因的相对mRNA水平因周期阶段而异，在动情前期水平最低，在动情间期第1天（即周期的黄体期）表达峰值最高，但在整个动情周期中，大鼠卵巢中均持续表达胃饥饿素基因。胃饥饿素免疫反应主要位于卵巢的黄体部分；在当前周期黄体的类固醇生成细胞以及所有退化黄体中均检测到强烈的免疫染色。事实上，使用假孕大鼠模型证实了胃饥饿素在黄体中的主要表达，在解剖的黄体组织中检测到最高的胃饥饿素mRNA水平。需要注意的是，胃饥饿素在卵巢中的表达模式的周期性似乎具有组织特异性，因为在胃中未检测到，在循环胃饥饿素水平方面也未观察到。此外，通过给予强效促性腺激素释放激素拮抗剂阻断排卵前促性腺激素高峰和排卵，可破坏卵巢胃饥饿素mRNA的周期性表达。最后，在整个妊娠期间，大鼠卵巢中持续检测到胃饥饿素mRNA表达，妊娠早期水平较高，妊娠后期表达较低。总之，我们的数据为胃饥饿素在大鼠周期性和妊娠卵巢中的表达提供了新证据。在动情周期和整个妊娠期间均检测到胃饥饿素表达模式的动态变化，从而提示胃饥饿素在卵巢中的表达受到精确调节。总体而言，我们目前的研究结果可能代表了体重稳态与女性生殖功能之间的另一个联系。
