Jackson G L, Wood S G, Kuehl D E
Department of Veterinary Biosciences, University of Illinois, Urbana 61802, USA.
Endocrinology. 2000 Nov;141(11):3940-5. doi: 10.1210/endo.141.11.7754.
Infusion of baclofen, a GABA(B) agonist, into the medial basal hypothalamus (MBH) of castrated rams rapidly increases LH pulse amplitude without altering pulse frequency. The objectives of this study were to determine whether baclofen infusion increased LH in testosterone (T)-treated and intact rams, the increased LH was due to increased GnRH release, and FSH secretion also was increased. In the first experiment we tested the main effects and interaction of baclofen and T on FSH and LH pulse patterns in castrated rams (n = 7). In the second experiment we determined whether baclofen affected GnRH and LH pulses in intact males. Microdialysis guide cannulae were implanted bilaterally into the MBH. After recovery of the animal from surgery, the MBH was perfused using concentric microdialysis probes (2-mm tip) with artificial cerebrospinal fluid (aCSF) for a 3-h control period followed by either aCSF or 1 mM baclofen for 4 h. Blood samples were taken at 10-min intervals. T suppressed mean LH concentrations (10.4 +/- 1.3 vs. 3.3 +/- 1.3 ng/ml) such that LH pulses were undetectable in some T-treated animals during the control period. The change (control period vs. drug infusion period) in mean LH was greater in response to baclofen than in response to aCSF and was not altered by T. The baclofen x T interaction was nonsignificant. Mean FSH was decreased by T, but was not altered by baclofen. In the second experiment hypophyseal portal blood was collected coincident with microdialysis. Infusion of baclofen into the MBH of intact males (n = 7) resulted within 1 h in the onset of frequent and robust GnRH pulses (0.10/h before baclofen vs. 1.57/h after baclofen) that were followed either immediately or gradually by coincident LH pulses. One interpretation is that baclofen acts downstream of the site of action of T. GABA(B) receptors may regulate pulse amplitude in both the presence and absence of T and regulate pulse frequency by modulating the inhibitory effect of T.
向去势公羊的内侧基底下丘脑（MBH）注入γ-氨基丁酸B（GABA(B)）激动剂巴氯芬，可迅速增加促黄体生成素（LH）脉冲幅度，而不改变脉冲频率。本研究的目的是确定在接受睾酮（T）治疗的公羊和未阉割公羊中，注入巴氯芬是否会增加LH，LH增加是否归因于促性腺激素释放激素（GnRH）释放增加，以及促卵泡生成素（FSH）分泌是否也会增加。在第一个实验中，我们测试了巴氯芬和T对去势公羊（n = 7）FSH和LH脉冲模式的主要影响及相互作用。在第二个实验中，我们确定了巴氯芬是否会影响未阉割雄性动物的GnRH和LH脉冲。将微透析引导套管双侧植入MBH。动物术后恢复后，使用同心微透析探针（尖端2毫米），用人工脑脊液（aCSF）对MBH进行3小时的对照期灌注，随后用aCSF或1 mM巴氯芬灌注4小时。每隔10分钟采集一次血样。T抑制了平均LH浓度（10.4±1.3对3.3±1.3 ng/ml），以至于在对照期，一些接受T治疗的动物中检测不到LH脉冲。与aCSF相比，巴氯芬引起的平均LH变化（对照期与药物灌注期）更大，且不受T的影响。巴氯芬×T的相互作用不显著。T降低了平均FSH，但巴氯芬未改变其水平。在第二个实验中，在进行微透析的同时采集垂体门脉血。向未阉割雄性动物（n = 7）的MBH注入巴氯芬，1小时内就出现了频繁且强烈的GnRH脉冲（注入巴氯芬前为0.10/小时，注入后为1.57/小时），随后立即或逐渐出现相应的LH脉冲。一种解释是，巴氯芬在T的作用位点下游起作用。GABA(B)受体可能在有T和无T的情况下都调节脉冲幅度，并通过调节T的抑制作用来调节脉冲频率。
