Victorian Institute of Animal Science, Department of Agriculture, Werribee, Victoria 3030, Australia. Prince Henry's Institute of Medical Research, P.O. Box 152, Clayton, Victoria 3168, Australia.
J Neuroendocrinol. 1992 Jun;4(3):365-74. doi: 10.1111/j.1365-2826.1992.tb00181.x.
In this study we tested the hypothesis that the negative feedback effects by testosterone on the secretion of luteinizing hormone (LH) in rams involves dopaminergic afferents to gonadotrophin-releasing hormone neurons operating via D(2) receptors in the non-breeding season. In the first experiment, three groups (n = 5) of rams were treated with an intravenous injection of vehicle or 10 or 20 mg of the dopaminergic D(2) antagonist pimozide and jugular venous samples were collected every 10 min for 3 h before and 3 h following treatment. The plasma was assayed for LH. Three groups of ewes (n = 4 to 5) were similarly treated. There were no significant effects of treatment of the rams with pimozide on the plasma concentrations of LH or LH pulse frequency or pulse amplitude and the response of individual rams in each group was inconsistent. In contrast, treatment of the ewes with 20 mg pimozide significantly (P<0.001) increased the mean (± SEM) plasma LH concentrations (pretreatment 0.37 ± 0.04; post-treatment 2.42±0.25 ng/ml) and decreased (P<0.001) the LH inter-pulse interval (pretreatment 180.0; post-treatment 88.0±11.1 min); the 10 mg dose of pimozide did not affect these parameters. In the second experiment, two groups of rams (n = 5) and ewes (n = 7) were treated with an intravenous injection of vehicle or 0.33 mg pimozide/kg liveweight and jugular venous samples were collected every 10 min for 2 h before and 6 h following treatment. As in the first experiment, the mean (± SEM) concentrations of plasma LH were not affected by treatment with pimozide in the rams (pretreatment 0.18 ± 0.25; post-treatment 0.43 ± 0.14 ng/ml) but were significantly (P<0.05) increased in the ewes (pretreatment 1.12±0.22; post-treatment 1.93 ± 0.23 ng/ml). In the third experiment, four adult rams were castrated and 3 weeks later each animal had two cannulae inserted to allow injection into the lateral cerebral ventricles. Vehicle or 100 μg pimozide was injected intracerebroventricularly and blood samples were collected as in the other experiments. A Latin Square design was used so that each animal received each treatment (n = 4). This procedure was repeated after the animals had been injected (intramuscularly) with 16 mg testosterone propionate twice daily for at least 7 days. Treatment with testosterone propionate significantly decreased (P < 0.001) the plasma concentrations of LH (pre-treatment 7.71±0.27; post-treatment 0.75 ± 0.27 ng/ml; mean ± SEM) and follicle-stimulating hormone (pre-treatment 79.61±8.47; post-treatment 42.53 ± 6.08 ng/ml; mean ± SEM) and increased the mean (± SEM) LH inter-pulse interval (53.14 ± 3.58 min pre-treatment and 292.5 ± 32.94 min post-treatment) but had no effect on the amplitude of LH pulses (pre-treatment 3.61 ± 0.36; post-treatment 1.86±1.76 ng; mean ± SEM). Pimozide had no effect on the plasma concentrations of gonadotrophins. These results suggest that, in the ram, dopaminergic neurons do not influence the gonadotrophin-releasing hormone neurons via D(2) receptors in the non-breeding season and are not involved in the negative feedback effect of testosterone on the secretion of gonadotrophins. Conversely, our data suggest that such a mechanism is integral to the negative feedback effects of oestradiol on LH in anoestrous ewes. Finally, it also appears that the steroid-independent suppression of the secretion of gonadotrophins during the non-breeding season in rams is not mediated via D(2) receptors.
在这项研究中，我们检验了这样一个假设，即在非繁殖季节，睾丸酮对促黄体激素（LH）分泌的负反馈作用涉及多巴胺能传入到促性腺激素释放激素神经元，通过 D2 受体发挥作用。在第一个实验中，三组（每组 5 只）公羊接受了静脉内注射载体或 10 或 20 毫克多巴胺 D2 拮抗剂匹莫齐特的治疗，在治疗前和治疗后 3 小时内每 10 分钟采集颈静脉样本。检测血浆 LH。三组母羊（每组 4 至 5 只）也进行了类似的处理。匹莫齐特处理对公羊的血浆 LH 浓度或 LH 脉冲频率或脉冲幅度没有显著影响，每组中个别公羊的反应不一致。相比之下，20 毫克匹莫齐特处理母羊显著（P<0.001）增加了平均（±SEM）血浆 LH 浓度（预处理 0.37±0.04；后处理 2.42±0.25ng/ml）并降低了（P<0.001）LH 脉冲间隔（预处理 180.0；后处理 88.0±11.1 分钟）；10 毫克剂量的匹莫齐特没有影响这些参数。在第二个实验中，两组公羊（每组 5 只）和母羊（每组 7 只）接受了静脉内注射载体或 0.33 毫克匹莫齐特/公斤活体重的治疗，并在治疗前和治疗后 6 小时内每 10 分钟采集颈静脉样本。与第一个实验一样，匹莫齐特处理对公羊的血浆 LH 浓度没有影响（预处理 0.18±0.25；后处理 0.43±0.14ng/ml），但在母羊中显著增加（P<0.05）（预处理 1.12±0.22；后处理 1.93±0.23ng/ml）。在第三个实验中，四只成年公羊被阉割，3 周后，每只动物都有两个套管插入，以便向侧脑室内注射。在其他实验中采集静脉血样，注射载体或 100 微克匹莫齐特。采用拉丁方设计，使每个动物接受每种处理（每组 4 只）。在动物每天两次肌肉注射 16 毫克丙酸睾酮至少 7 天后，重复此程序。睾酮丙酸酯处理显著降低（P<0.001）血浆 LH 浓度（预处理 7.71±0.27；后处理 0.75±0.27ng/ml；均值±SEM）和卵泡刺激素（预处理 79.61±8.47；后处理 42.53±6.08ng/ml；均值±SEM），并增加了 LH 脉冲间隔的平均（±SEM）（预处理 53.14±3.58 分钟，后处理 292.5±32.94 分钟），但对 LH 脉冲幅度没有影响（预处理 3.61±0.36；后处理 1.86±1.76ng；均值±SEM）。匹莫齐特对促性腺激素的血浆浓度没有影响。这些结果表明，在公羊中，多巴胺能神经元在非繁殖季节不通过 D2 受体影响促性腺激素释放激素神经元，也不参与睾丸酮对促性腺激素分泌的负反馈作用。相反，我们的数据表明，这种机制是雌二醇对非发情母羊 LH 负反馈作用的组成部分。最后，似乎在公羊中，非繁殖季节促性腺激素分泌的类固醇非依赖性抑制也不是通过 D2 受体介导的。
