Shiota K, Yoshida K, Noguchi C, Nakayama R
Acta Endocrinol (Copenh). 1984 May;106(1):71-8. doi: 10.1530/acta.0.1060071.
Using dispersed and primarily cultured cells of rat pituitary glands, thyrotrophin (TSH) release by TSH-releasing hormone (TRH) and an analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L- prolinamide (DN-1417) which is more potent than TRH on central nervous system behavioural paradigms, was examined under conditions of static incubation and superfusion. Static incubations of the cells with different concentrations of DN-1417 (10(-7)-10(-4) M) and TRH (10(-10)-10(-6) M) resulted in a dose-related increase of TSH release and the response to both peptides, in logarithmic doses, was in parallel. The potency of DN-1417 related to TSH release was 0.14-0.26% that of TRH. Maximal TSH release induced by DN-1417 (10(-5) M) was slightly but significantly greater than that by TRH (10(-7) M). In the presence of 3-isobutyl-1-methylxanthine, the TSH response to either of the peptides was augmented, and the difference in the maximal TSH release by either peptide became insignificant, suggesting that TRH as well as DN-1417 act through the same mechanism of mediation by the cyclic nucleotides. In the superfusion study, a biphasic profile of TSH release was observed during a continuous exposure (100 min) to maximal doses of either the analogue or TRH. The biphasic release of TSH was thought to be specific to TRH action because high K+ produced a different profile of the release. These results indicate that the potency of DN-1417 in TSH release is considerably lower than that of TRH, and also suggest that the direct action of DN-1417 on TSH release is qualitatively similar to that of TRH.
利用大鼠垂体分散的原代培养细胞，在静态孵育和灌流条件下，检测促甲状腺激素释放激素（TRH）及其类似物γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺（DN-1417，在中枢神经系统行为范式中比TRH更有效）诱导的促甲状腺激素（TSH）释放。用不同浓度的DN-1417（10⁻⁷ - 10⁻⁴M）和TRH（10⁻¹⁰ - 10⁻⁶M）对细胞进行静态孵育，导致TSH释放呈剂量相关增加，并且两种肽的对数剂量反应呈平行关系。与TSH释放相关的DN-1417的效力是TRH的0.14 - 0.26%。DN-1417（10⁻⁵M）诱导的最大TSH释放略高于但显著高于TRH（10⁻⁷M）诱导的最大TSH释放。在存在3-异丁基-1-甲基黄嘌呤的情况下，两种肽的TSH反应均增强，并且两种肽诱导的最大TSH释放差异变得不显著，这表明TRH和DN-1417通过环核苷酸的相同介导机制起作用。在灌流研究中，在持续暴露（100分钟）于类似物或TRH的最大剂量期间，观察到TSH释放呈双相模式。TSH的双相释放被认为是TRH作用所特有的，因为高钾产生了不同的释放模式。这些结果表明，DN-1417在TSH释放方面的效力远低于TRH，并且还表明DN-1417对TSH释放的直接作用在性质上与TRH相似。
