Celik Onder, Celik Nilufer, Aydin Suleyman, Aygun Banu Kumbak, Haberal Esra Tustas, Kuloglu Tuncay, Ulas Mustafa, Aktun Lebriz Hale, Acet Mustafa, Celik Sudenaz
Horm Mol Biol Clin Investig. 2016 Feb;25(2):121-8. doi: 10.1515/hmbci-2015-0050.
Acylated ghrelin (AG) effect on GnRH secretion is mediated, at least in part, by GH secreta-gogue receptor (GHS-R) which is present in the GnRH neurons. As the acylation is mandatory for binding to GHS-R, unacylated isoform of ghrelin (UAG) action on gonadotropin secretion is likely to be mediated by other receptors or mediators that have not been identified yet. UAG, therefore, may act partially via a GHS-R-independent mechanism and inhibitory impact of UAG on GnRH neurons may be executed via modulation of other neuronal networks. Ghrelin and gonadotropin inhibitory hormone (GnIH), two agonistic peptides, have been known as important regulators of reproductive events. Potential impact of ghrelin on the activity of GnIH neurons is not exactly known. Both GnIH and ghrelin are potent stimulators of food intake and inhibitors of gonadotropin release. By binding G-protein coupled GnIH receptor (GnIH-R), GPR147, which is located in the human gonadotropes and GnRh neurons, GnIH exerts an inhibitory effect on both GnRH neurons and the gonadotropes. The GnIH-GPR147 system receives information regarding the status of energy reservoir of body from circulating peptides and then transfers them to the kisspeptin-GnIH-GnRH network. Due to wide distribution of this network in brain GnIH neurons may project on ghrelin neurons in the arcuate nucleus and contribute to the regulation of UAG's central effects or vice versa. Together, the unidentified ghrelin receptor in the hypothalamus and hypophysis may be GnIH-R. Therefore, it is reasonable that ghrelin may act on both hypothalamus and hypophysis via GnIH-GPR147 system to block gonadotropin synthesis and secretion.
酰化胃饥饿素（AG）对促性腺激素释放激素（GnRH）分泌的影响至少部分是由存在于GnRH神经元中的生长激素促分泌素受体（GHS-R）介导的。由于酰化对于与GHS-R结合是必需的，胃饥饿素的未酰化异构体（UAG）对促性腺激素分泌的作用可能是由尚未确定的其他受体或介质介导的。因此，UAG可能部分通过不依赖GHS-R的机制发挥作用，并且UAG对GnRH神经元的抑制作用可能是通过调节其他神经网络来实现的。胃饥饿素和促性腺激素抑制激素（GnIH）这两种激动肽，已被认为是生殖活动的重要调节因子。胃饥饿素对GnIH神经元活性的潜在影响尚不完全清楚。GnIH和胃饥饿素都是食物摄入的强效刺激剂和促性腺激素释放的抑制剂。GnIH通过与位于人促性腺细胞和GnRh神经元中的G蛋白偶联GnIH受体（GnIH-R）GPR147结合，对GnRH神经元和促性腺细胞均发挥抑制作用。GnIH-GPR147系统从循环肽中接收有关身体能量储备状态的信息，然后将其传递给亲吻素-GnIH-GnRH网络。由于该网络在大脑中广泛分布，GnIH神经元可能投射到弓状核中的胃饥饿素神经元上，并有助于调节UAG的中枢效应，反之亦然。下丘脑和垂体中未确定的胃饥饿素受体可能是GnIH-R。因此，胃饥饿素可能通过GnIH-GPR147系统作用于下丘脑和垂体，以阻断促性腺激素的合成和分泌是合理的。
