Larco Darwin O, Williams Melissa, Schmidt Lauren, Sabel Nick, Lange Jason, Woller Michael J, Wu T J
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Endocrine. 2015 Jun;49(2):470-8. doi: 10.1007/s12020-014-0492-7. Epub 2014 Dec 17.
Given the central role of the decapeptide gonadotropin-releasing hormone (GnRH) in reproductive function, our long-term objective is to delineate the underlying mechanism regulating these reproductive processes. The outcome of GnRH secretion is in part dependent on the proteolytic metabolism of this decapeptide. In contrast to the belief that the metabolism of GnRH serves only as a degradative process that removes excess GnRH, we have shown that a metabolite of the decapeptide, GnRH-(1-5), can directly regulate GnRH gene expression and reproductive behavior. To further characterize the effect of GnRH-(1-5) on GnRH neuronal function, we determined whether GnRH-(1-5) can directly regulate GnRH secretion and pulsatility using an in vitro perifusion system. We compared the effect of GnRH-(1-5) on GnRH secretion in the immortalized GnRH neuron (GT1-7 cell line), whole rat hypothalamic explant, and enzymatically dispersed rat hypothalamic cells. Tissue preparations were perifused continuously for 9 h during which a 3-h challenge with GnRH-(1-5) was administered (4-6 h). The results show that treatment with GnRH-(1-5) increased (p < 0.05) the mean GnRH secretion and the amplitude of the pulses but not the pulse frequency. The present study supports the notion that GnRH-(1-5) is functionally capable of regulating the reproductive neuroendocrine system.
鉴于十肽促性腺激素释放激素（GnRH）在生殖功能中的核心作用，我们的长期目标是阐明调节这些生殖过程的潜在机制。GnRH分泌的结果部分取决于该十肽的蛋白水解代谢。与认为GnRH的代谢仅作为去除过量GnRH的降解过程的观点相反，我们已经表明十肽的一种代谢产物GnRH-(1-5)可以直接调节GnRH基因表达和生殖行为。为了进一步表征GnRH-(1-5)对GnRH神经元功能的影响，我们使用体外灌流系统确定GnRH-(1-5)是否可以直接调节GnRH分泌和脉冲性。我们比较了GnRH-(1-5)对永生化GnRH神经元（GT1-7细胞系）、大鼠下丘脑全组织外植体和酶分散的大鼠下丘脑细胞中GnRH分泌的影响。组织制剂连续灌流9小时，在此期间给予GnRH-(1-5) 3小时的刺激（4-6小时）。结果表明，用GnRH-(1-5)处理可增加（p < 0.05）GnRH的平均分泌量和脉冲幅度，但不增加脉冲频率。本研究支持GnRH-(1-5)在功能上能够调节生殖神经内分泌系统的观点。
