Meyer D C, McRee C, Jacobs M
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501.
Brain Res Bull. 1992 Jun;28(6):853-60. doi: 10.1016/0361-9230(92)90205-c.
The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5-HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) treated rats using in vitro superfusion techniques. Regularly cycling female Holtzman rats (250-300 g) were maintained on a photoperiod of 0500-1900 h light at 22 +/- 2 degrees C. Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150 micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2 receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist Lilly 53857 (1 x 10(-6) M or 1 x 10(-5) M) did not increase LHRH release above control levels. Neither 5-HT nor quipazine had a significant effect on LHRH release at 1 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(-5) M) significantly (p less than 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT1 receptor plays a role in LHRH release and this effect may be related to the opposing effects of postsynaptic and autoreceptors. However, the failure of Lilly 53857 to reproduce the stimulatory effect of ketanserin on LHRH release suggests that 5-HT2 receptors in the MBH-POA-SCN may not modify LH release during the estrous cycle.
本实验采用体外灌流技术，研究了酮色林[5-羟色胺-2（5-HT2）拮抗剂]和8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）（5-HT1激动剂）对去卵巢（OVX）、经雌二醇（E2）处理的大鼠内侧基底下丘脑-视前区-视交叉上核区域（MBH-POA-SCN）促黄体生成激素释放激素（LHRH）体外释放的影响。正常发情周期的雌性霍尔茨曼大鼠（250 - 300 g）饲养于光照周期为0500 - 1900 h、温度为22±2℃的环境中。大鼠在25 - 30日龄时进行去卵巢手术，并在体外灌流前48 h皮下植入含150μg E2/ ml芝麻油的硅橡胶E2植入物。在进行Krebs-Ringer磷酸盐（KRP）灌流的对照期后，酮色林（5-HT2受体拮抗剂，1×10⁻⁶ M）显著增加了LHRH的释放（p < 0.05）。随后灌流5-羟色胺（5-HT，1×10⁻⁸ M）显著降低（p < 0.05）了酮色林对LHRH释放的作用。5-HT2拮抗剂Lilly 53857（1×10⁻⁶ M或1×10⁻⁵ M）并未使LHRH释放增加至对照水平以上。5-HT和喹哌嗪在1×10⁻⁶ M时对LHRH释放均无显著影响。灌流8-OH-DPAT（5-HT1受体激动剂，1×10⁻⁵ M）显著（p < 0.01）增加了LHRH的释放，但随后灌流8-OH-DPAT + 吲哚洛尔（5-HT1a、1b和β肾上腺素能受体混合拮抗剂，1×10⁻⁶ M）或单独灌流吲哚洛尔对LHRH释放均无影响。这些结果表明，5-HT1受体在LHRH释放中起作用，且这种作用可能与突触后受体和自身受体的相反作用有关。然而，Lilly 53857未能重现酮色林对LHRH释放的刺激作用，提示MBH-POA-SCN中的5-HT2受体可能在发情周期中不调节促黄体生成素（LH）的释放。
