Wilson Andrea C, Meethal Sivan Vadakkadath, Bowen Richard L, Atwood Craig S
University of Wisconsin-Madison, Department of Medicine, and Geriatric Research, Education and Clinical Center, William S Middleton Memorial Veterans Administration Hospital, 2500 Overlook Terrace, Madison, WI 53705, USA.
Expert Opin Investig Drugs. 2007 Nov;16(11):1851-63. doi: 10.1517/13543784.16.11.1851.
Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide acetate suppresses gonadotrope secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses gonadal sex steroid production. In addition, leuprolide acetate is presently being tested for the treatment of Alzheimer's disease, polycystic ovary syndrome, functional bowel disease, short stature, premenstrual syndrome and even as an alternative for contraception. Mounting evidence suggests that GnRH agonist suppression of serum gonadotropins may also be important in many of the clinical applications described above. Moreover, the presence of GnRHR in a multitude of non-reproductive tissues including the recent discovery of GnRHR expression in the hippocampi and cortex of the human brain indicates that GnRH analogs such as leuprolide acetate may also act directly via tissue GnRHRs to modulate (brain) function. Thus, the molecular mechanisms underlying the therapeutic effect of GnRH analogs in the treatment of these diseases may be more complex than originally thought. These observations also suggest that the potential uses of GnRH analogs in the modulation of GnRH signaling and treatment of disease has yet to be fully realized.
醋酸亮丙瑞林是一种合成九肽，是一种有效的促性腺激素释放激素受体（GnRHR）激动剂，用于多种临床应用，包括治疗前列腺癌、子宫内膜异位症、子宫肌瘤、中枢性性早熟以及体外受精技术。作为其基本作用机制，醋酸亮丙瑞林抑制促性腺激素细胞分泌促黄体生成素和促卵泡生成素，进而抑制性腺甾体激素的产生。此外，目前正在对醋酸亮丙瑞林进行测试，以用于治疗阿尔茨海默病、多囊卵巢综合征、功能性肠病、身材矮小、经前综合征，甚至作为一种避孕替代方法。越来越多的证据表明，GnRH激动剂对血清促性腺激素的抑制作用在上述许多临床应用中可能也很重要。此外，在包括最近发现人脑海马体和皮质中存在GnRHR表达在内的多种非生殖组织中都存在GnRHR，这表明诸如醋酸亮丙瑞林之类的GnRH类似物也可能通过组织GnRHR直接发挥作用来调节（大脑）功能。因此，GnRH类似物在治疗这些疾病中的治疗作用的分子机制可能比最初认为的更为复杂。这些观察结果还表明，GnRH类似物在调节GnRH信号和治疗疾病方面的潜在用途尚未得到充分认识。
