Nishi N, Coy D H, Coy E J, Arimura A, Schally A V
J Reprod Fertil. 1976 Sep;48(1):119-24. doi: 10.1530/jrf.0.0480119.
Peptide antagonists of LH-RH, [D-Phe2, D-Phe6]-LH-RH, [D-Phe2,D-Leu6]-LH-RH, [D-Phe2, D-Ala6]-LH-RH, [D-Phe2, D-Phe3,D-Phe6]-LH-RH, [DesHis2, D-Leu6]-LH-RH, and [DesHis2, D-Phe6]-LH-RH, were examined for their ability to suppress LH-RH-induced ovulation in phenobarbital-blocked hamsters and Nembutal-blocked rats. All of these peptides, with the exception of [DesHis2, Phe6]- LH-RH suppressed ovulation to various degrees, but alos exhibited various degrees of agonistic activities. Complete suppression of ovulation was achieved in rats with 3 mg [D-Phe2,Phe3,-D-Phe6]-LH-RH given in 4 divided doses at 30-min intervals starting 2 hr before the LH-RH injection. It was found that LH levels had to be lower than 5 ng/ml (control: 20-9 ng/ml) to suppress ovulation. However, the extent of suppression of ovulationdid not correlate with the serum LH levels less than 5 ng/ml. The incidence of ovulation induced by the intrinsic LH-RH activity of some of these analogues was similar to or greater than that resulting from administration of LH-RH plus analogue, suggesting that the activity of LH-RH itself was eliminated by pretreatment with the analogues.
促黄体生成素释放激素（LH-RH）的肽拮抗剂，[D-苯丙氨酸2，D-苯丙氨酸6]-LH-RH、[D-苯丙氨酸2，D-亮氨酸6]-LH-RH、[D-苯丙氨酸2，D-丙氨酸6]-LH-RH、[D-苯丙氨酸2，D-苯丙氨酸3，D-苯丙氨酸6]-LH-RH、[去组氨酸2，D-亮氨酸6]-LH-RH和[去组氨酸2，D-苯丙氨酸6]-LH-RH，在苯巴比妥阻断的仓鼠和戊巴比妥阻断的大鼠中，被检测其抑制LH-RH诱导排卵的能力。所有这些肽，除了[去组氨酸2，苯丙氨酸6]-LH-RH外，均不同程度地抑制了排卵，但也表现出不同程度的激动活性。在LH-RH注射前2小时开始，以30分钟的间隔分4次给予3毫克[D-苯丙氨酸2，苯丙氨酸3，-D-苯丙氨酸6]-LH-RH，可完全抑制大鼠排卵。发现LH水平必须低于5纳克/毫升（对照组：20 - 9纳克/毫升）才能抑制排卵。然而，排卵抑制程度与血清LH水平低于5纳克/毫升并无相关性。这些类似物中一些因自身LH-RH活性诱导排卵的发生率与给予LH-RH加类似物所导致的发生率相似或更高，这表明类似物预处理消除了LH-RH本身的活性。
