Mechanism of gene expression by androgen receptor in rat and mouse submandibular glands

类固醇受体从非转化状态向转化状态的转化，称为转化，被认为是类固醇激素作用的关键过程。转化的受体激活靶细胞中的特定基因。类固醇激素受体从DNA-未结合状态到DNA-结合状态的转化可以通过短暂加热、暴露于盐或ATP和凝胶层析来诱导。一般来说，未转化的受体通过加入硫酸鱼精蛋白选择性沉淀。我们发现，负责非转化受体与鱼精蛋白相互作用的成分是一种88-kDa的蛋白质，该88-kDa的蛋白质与海拉细胞和酵母的热休克蛋白90的氨基酸组成几乎相同，类固醇转化的受体复合物与核受体位点相互作用，但目前尚不清楚染色质结构如何改变以促进基因表达。[^3H]雄激素预标记的胞浆雄激素受体与小鼠下颌下腺粗核相互作用，受体的激活是这种相互作用的先决条件。在雌性小鼠体内给予[^3H]雄激素后，在从颌下腺组织中纯化的细胞核中发现了放射活性，用微球菌核酸酶进一步消化[^3H]雄激素标记的纯化细胞核。雄激素受体存在于溶解的活性染色质组分中，其中含有单核体和双核体。通过体外交换试验，内源性雄激素受体复合物与染色质结合位点在完整的男性被发现在微球菌核酸酶消化后的溶解级分，而这样的复合物没有发现在女性。这些结果表明，雄激素受体易位到细胞核，并成为与染色质和这种协会优先敏感的微球菌核酸酶。

Conversion of steroid receptors from the nontransformed to transformed state, called transformation, is thought to be a key process of the steroid hormone action. Transformed receptors activate the specific genes in target cells. Transformation of steroid hormone receptor from a DNA-unbound state to a DNA-bound state can be induced by brief heating, exposure to salt, or ATP, and gel chromatography. IN general, nontransformed receptor is precipitated selectively by the addition of protamine sulfate. We found that the component responsible for the interection between the nontransformed receptor and protamine is an 88-kDa protein and this 88-kDa protein is almost the same as those of heat-shock protein 90 of hela cells and yeast for the amino acid composition.The steroid-transformed receptor complex interacts with nuclear acceptor sites, but it remains unclear how the structure of chromatin is changed for gene expression. Cytosol androgen receptor prelabeled with [^3H]androgen interacted with the crude nuclei in mouse submandibular gland and activation of the receptor was prerequisite for this interaction. After in vivo administration of [^3H]androgen to female mice, redioactivities were found in the nuclei purified from submandibular gland tissues and the [^3H]androgen-labeled purified nuclei were further digested with micrococcal nuclease. the androgen receptor was found in solubilized, active chromatin fractions which contained mono- and dinucleosomes. By an in vitro exchange assay, endogenous androgen-receptor complexes associated with chromatin binding sites in intact males were found in the solubilized fraction after micrococcal nuclease digestion, whereas such complexes were not found in females. These results suggest that the androgen receptors translocated to the nuclei and became associated with chromatin and that this association preferentially sensitive to micrococcal nuclease.