Milenkovic L, Lyson K, Aguila M C, McCann S M
Department of Physiology, University of Texas, Southwestern Medical Center at Dallas 75235-9040.
Neuroendocrinology. 1992 Nov;56(5):674-9. doi: 10.1159/000126292.
Thymosin alpha 1 (T alpha 1) is a well-characterized immunopotentiating polypeptide originally isolated from calf thymus. We have recently shown in vivo, probable hypothalamic effects of T alpha 1 to decrease the release of the pituitary hormones, TSH, PRL and ACTH from the pituitary gland. Therefore, in the present study we evaluated the effect of the peptide on the release of hypothalamic regulatory hormones: thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), as well as somatostatin (SRIH), from medial basal hypothalamic (MBH) fragments incubated in vitro. After a preliminary time-course study indicated that a 30-min incubation period was optimal, it was used for all the other experiments. At the end of the incubation the tissue was still able to respond to a depolarizing K+ concentration for 15 min by a 4-fold increase of TRH concentration compared to control basal release during the preceding 30 min. T alpha 1 was shown to inhibit the release of TRH and CRH from MBH fragments incubated in vitro with a minimal effective dose (MED) of 10(-11) M. SRIH and CRH release was also inhibited but the MED for these peptides was 10(-9) M. The relative responsiveness to the action of T alpha 1 was TRH greater than CRH, which was greater than SRIH. This correlated with our previous in vivo results for pituitary hormone release, except in the case of SRIH since we previously did not detect any significant effect of the peptide on growth hormone release. Finally, we evaluated the possible involvement of other neurotransmitters in the effect of T alpha 1 on TRH release.(ABSTRACT TRUNCATED AT 250 WORDS)
胸腺素α1(Tα1)是一种特性明确的免疫增强多肽,最初从小牛胸腺中分离得到。我们最近在体内研究中发现,Tα1可能对下丘脑产生影响,从而减少垂体激素促甲状腺激素(TSH)、催乳素(PRL)和促肾上腺皮质激素(ACTH)从垂体的释放。因此,在本研究中,我们评估了该多肽对体外培养的内侧基底部下丘脑(MBH)片段释放下丘脑调节激素的影响,这些激素包括促甲状腺激素释放激素(TRH)、促肾上腺皮质激素释放激素(CRH)以及生长抑素(SRIH)。在一项初步的时间进程研究表明30分钟的孵育期最为适宜后,该孵育期被用于所有其他实验。孵育结束时,与前30分钟的对照基础释放相比,组织在接下来的15分钟内仍能够对去极化的钾离子浓度作出反应,使TRH浓度增加4倍。结果显示,Tα1能够抑制体外培养的MBH片段释放TRH和CRH,最小有效剂量(MED)为10^(-11) M。SRIH和CRH的释放也受到抑制,但这些多肽的MED为10^(-9) M。对Tα1作用的相对反应性为TRH大于CRH,CRH大于SRIH。这与我们之前关于垂体激素释放的体内研究结果相关,除了SRIH的情况,因为我们之前未检测到该多肽对生长激素释放有任何显著影响。最后,我们评估了其他神经递质可能参与Tα1对TRH释放的影响。(摘要截选至250词)