Mechanisms of hormonal regulations in brown adipose tissue of developing rats.
Mechanisms of hormonal regulations in brown adipose tissue of developing rats.
复制标题
发育中大鼠棕色脂肪组织的激素调节机制。
DOI：
10.1139/o84-085
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
J. Skala
中科院分区：
文献类型：
--
作者：
J. Skala
在新生儿中，棕色脂肪组织的主要功能之一--非颤抖产热的必要性得到了强调。相应地，大鼠的棕色脂肪在出生后表现出非常明显的形态和功能成熟过程，其分化和生热能力在出生后1-2周内达到顶峰，并在后来的生活中经历了进化的变化。随后的脱分化过程可以通过长期将动物暴露在寒冷的环境温度下(冷习服)来防止或逆转。对组织成熟过程和叠加的急性热产生的调节都是由激素调节的。因此，脂肪细胞膜内的激素受体系统和连接最初的激素刺激及其最终的细胞内效应的分子事件序列(S)是相当重要的。发育中的大鼠棕色脂肪细胞具有肾上腺素受体，可分为β1(与腺苷环化酶相连)和α2(可能与鸟苷环化酶相连)，多种形式的环核苷酸依赖和独立的蛋白激酶，一种蛋白激酶抑制剂，以及至少两种不同的与三种磷酸蛋白磷酸酶调节剂相关的磷酸蛋白磷酸酶。在过去的十年里，我们小组对这些调节成分的特征和发育变化进行了相当详细的研究。研究结果揭示了荷尔蒙反应的几个靶点系统。在个体发育过程中，蛋白质磷酸化和去磷酸化是调节棕色脂肪细胞功能和增殖活性的主要分子机制，这一假设得到了强有力的支持。
The need for nonshivering heat production, a principal function of brown adipose tissue, is accentuated in neonates. Accordingly, brown fat in the rat exhibits a very pronounced process of morphological and functional maturation perinatally, reaches a peak in its differentiation and heat-generating capacity within 1-2 weeks after birth, and undergoes involutive changes later in life. The later process of dedifferentiation can be either prevented or reversed by exposing the animals to cold ambient temperature for a prolonged period of time (cold acclimatization). The regulation of both the tissue maturation processes and the superimposed acute heat production are hormone mediated. Thus, the hormone receptor system within the adipocyte membrane and the sequence of molecular events interconnecting the initial hormonal stimulus with its final intracellular effect(s) are of considerable importance. The brown adipocytes of developing rats possess adrenoreceptors that can be pharmacologically classified as beta 1 (linked to adenylate cyclase) and alpha 2 (possibly linked to guanylate cyclase), multiple forms of cyclic nucleotide dependent and independent protein kinases, a protein kinase inhibitor, and at least two distinct phosphoprotein phosphatases associated with three phosphoprotein phosphatase modulators. The characteristics and developmental alterations of these regulatory components were studied in considerable detail by our group during the past decade. The results uncovered several target systems for ontogenic modifications of hormonal responses. Strong support was obtained for the hypothesis that protein phosphorylation and dephosphorylation is a major molecular mechanism involved in the regulation of both the brown adipocyte function and its proliferative activity during ontogenic development.