CHARACTERIZATION OF HYPOTHALAMO-LYMPHO--THYROID AXIS
下丘脑-淋巴-甲状腺轴的特征
基本信息
- 批准号:2266744
- 负责人:
- 金额:$ 9.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1990
- 资助国家:美国
- 起止时间:1990-09-17 至 1995-08-31
- 项目状态:已结题
- 来源:
- 关键词:disease /disorder model flow cytometry genetic regulation hormone biosynthesis hormone regulation /control mechanism human subject human tissue hypothalamic pituitary axis immunofluorescence technique immunoregulation laboratory mouse lymphocyte messenger RNA model design /development neuroimmunomodulation radioimmunoassay second messengers thymectomy thyrotropin thyrotropin releasing hormone
项目摘要
Recent evidence documents relationships between the immune, endocrine and
neural systems. A molecular basis for these interactions is an embryonic
commonality and the production of similar signal molecules. Therefore
manifestations and alterations in one systems result in manifestations and
alterations in the other systems. In vivo support for this concept are the
reports that athymic or thymectomized mice present with severe endocrine
disorders such as hypothyroidism. Thyrotropin (TSH) is a pituitary
molecule regulated positively by thyrotropin releasing hormone (TRH) and
negatively by feedback from the thyroid gland in the form of thyroid
hormones, T3 and T4. Recent studies have documented that the immune system
both produces immunoreactive TSH as well responds to TSH and TRH. Based on
the afforementioned rationale, we have postulated that there exists a
hypothalamic-lymphoid-thyroid (HLT) axis. We have partially developed and
preliminarily tested a novel in vitro system (hypothalamic-pituitary-
thyroid --HPT axis). We have shown that cells of the immune system respond
in vitro to TRH by releasing ir-TSH. We have also shown in a small sample
that in individuals with a reduced or "blunted" in vivo TSH response to
exogenous TRH administration, there is generally a blunted in vitro ir-TSH
response. Similarily, for those individuals with a normal in vivo response
to TRH, there is also an increase in vitro ir-TSH production. Based on our
preliminary data, we have gone one step further in our hypothesis and
proposed that leukocytes, serving as models of the HPT axis, reflect
defects in the neuroendocrine axis as similar defects in the HLT axis. In
this project, we plan to further characterize the parallelness of the HLT
with the HPT axis by using inbred mouse models of defined thyroid and T
cell function. Using this well controlled animal model system, we may ask
mechanistic questions concerning the regulation of the genes for ir-TSH and
the status of putative TRH receptors on cells of the immune system in
relation to their putative counterparts in the neuroendocrine system. This
type of system will establish the validity of using the HLT as a peripheral
model for the HPT axis. This system may have ramifications in
endocrinology, immunology as well as neuroscience and neurobehavior. Our
system may be useful for studying the molecular and mechanistic basis for
interactions between the immune and neuroendocrine systems. This research
may provide a rationale for holistic approaches to mental health and
susceptibility to endocrine disorder, infection, cancer and autoimmune
disease processes.
最近的证据证明了免疫、内分泌和
神经系统 这些相互作用的分子基础是一个胚胎
共同性和相似信号分子的产生。 因此
一个系统的表现和改变导致表现和
其他系统的变化。 体内支持这一概念的是
报告称,无胸腺或胸腺切除的小鼠出现严重的内分泌失调,
甲状腺功能减退症等疾病。 促甲状腺激素(TSH)是一种垂体
由促甲状腺激素释放激素(TRH)积极调节的分子,
通过甲状腺的反馈,
激素T3和T4 最近的研究表明,免疫系统
两者都产生免疫反应性TSH,并对TSH和TRH有反应。 基于
根据前面提到的基本原理,我们假设存在一个
下丘脑-淋巴样-甲状腺(HLT)轴。 我们已经部分开发了,
初步测试了一种新的体外系统(下丘脑-垂体-
甲状腺-HPT轴)。 我们已经证明免疫系统的细胞
在体外通过释放ir-TSH对TRH的作用。 我们还在一个小样本中显示,
在体内TSH反应降低或“钝化”的个体中,
外源性TRH给药后,体外ir-TSH
反应 类似地,对于具有正常体内反应的那些个体,
对TRH,也有体外ir-TSH产生的增加。 基于我们
根据初步数据,我们在假设中又向前迈进了一步,
提出,白细胞,作为模型的HPT轴,反映
神经内分泌轴的缺陷与HLT轴的缺陷相似。 在
在这个项目中,我们计划进一步描述HLT的并行性
与HPT轴通过使用近交系小鼠模型的定义甲状腺和T
细胞功能 使用这种控制良好的动物模型系统,我们可能会问,
关于ir-TSH基因调节的机制问题,
免疫系统细胞上假定的TRH受体的状态,
与神经内分泌系统中的假定对应物的关系。 这
一种类型的系统将确定使用HLT作为外围设备的有效性
HPT轴的模型。 这个系统可能会产生一些影响,
内分泌学、免疫学以及神经科学和神经行为学。 我们
系统可能有助于研究分子和机械基础,
免疫系统和神经内分泌系统之间的相互作用。 本研究
可能为心理健康的整体方法提供理论基础,
对内分泌紊乱、感染、癌症和自身免疫的易感性
疾病过程。
项目成果
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{{ truncateString('LEE-NIEN L CHAN', 18)}}的其他基金
IN VITRO NEUROENDOCRINE T CELL LINE PRODUCTION OF TSH
体外神经内分泌 T 细胞系生产 TSH
- 批准号:
2266478 - 财政年份:1989
- 资助金额:
$ 9.64万 - 项目类别:
MULTIGENERATION EFFECTS OF PATERNAL MUTAGEN EXPOSURE
父本诱变剂暴露的多代效应
- 批准号:
3252091 - 财政年份:1988
- 资助金额:
$ 9.64万 - 项目类别:
MULTIGENERATION EFFECTS OF PATERNAL MUTAGEN EXPOSURE
父本诱变剂暴露的多代效应
- 批准号:
3252094 - 财政年份:1988
- 资助金额:
$ 9.64万 - 项目类别:
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