Growth hormone gene regulation: a paradigm for cell-type-specific gene activation.
Growth hormone gene regulation: a paradigm for cell-type-specific gene activation.
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生长激素基因调控：细胞类型特异性基因激活的范例。
DOI：
10.1016/0168-9525(90)90100-k
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Theill,LE
中科院分区：
文献类型：
--
作者：
Karin,M;Castrillo,JL;Theill,LE
生长激素（GH）基因在垂体前叶的特化细胞内特异性表达。ghf - 1是一种在垂体前叶特异性表达的同源结构域蛋白，它在GH基因激活中起着核心作用。第一次出现是在老鼠的胚胎期8.5天（其他哺乳动物的时间不同），表现为口腔内胚层的内陷。到12岁时，拉特克眼袋从口腔上皮中分离出来，成为一个独立的结构，启动了细胞快速增殖的程序。其腹侧上皮为垂体前原，背侧上皮为垂体中间叶。细胞分化产生不同的激素分泌细胞，如图15-16所示。另外两种被称为嗜酸细胞和嗜碱性细胞的前体由原始干细胞形成。嗜酸细胞是产生gh的生长营养细胞和产生催乳素的乳营养细胞的祖细胞，而嗜碱性细胞则产生专门产生促肾上腺皮质激素、促甲状腺激素、促卵泡激素或促黄体生成素的细胞。另一方面，中间体垂体专门合成各种肽激素，这些激素来源于促黑素皮质素基因。大多数催乳素表达细胞似乎来源于产生gh的前体。完成了。通过将gh -白喉毒素和gh -胸苷激酶融合基因插入转基因小鼠的种系中，也可以消除大部分乳营养物质sh，~ z，但仍有一小部分乳营养物质逃脱了消融1。泌乳胸苷激酶基因的表达不导致消融~ 2。这些观察结果支持了图1所示的生长营养细胞和乳营养细胞之间的线性关系，并表明大多数表达催乳素的细胞是有丝分裂后的生长营养细胞。尽管有共同的前体，但直到出生后10-12天才能在小鼠中检测到催乳素的表达，而生长激素在第16期首次检测到表达（参考文献13）。因此，这两个基因不太可能被一个共同因素协调激活。
The growth hormone (GH) gene is spedfically expressed within specialized cells of the anterior pituitary. The central role in GH gene activation is played by GHF-I, a homeodomain protein that is itself specifically expressed in the anterior pituitary. that first appears at embryonic day (ed) 8.5 of the mouse (timing is different in other mammals), as an invagination of the oral endoderm. By ed 12, Rathke's pouch detaches from the oral epithelium and becomes an individual structure, initiating a program of rapid cell proliferation9. Its ventral epithelium serves as the anterior pituitary anlagen while the dorsal epithelium generates the intermediate lobe of the pituitary. Cytodifferentiation gives rise to different hormone-producing cells that appear on ed 15-16. Two more committed precursors known as acidophils and basophils are formed from the primordial stem cell. The acidophils are the progenitors for both the GH-producing somatotrophs and prolactin-producing lactotrophs, while the basophils give rise to cells that specialize to produce either adrenocorticotropin, thyroid-stimulating hormone, follicle-stimulating hormone or luteinizing hormone I0. The intermediate, pituitary, on the other hand, specializes in the synthesis of various peptide hormones derived from the proopiomelanocortin gene.Most of the prolactin-expressing cells appear to be derived from GH-producing precursors. Complete. ablation of somatotrophs by expression of GH-diphtheria toxin and GH-thymidine kinase fusion genes inserted into the germ line of transgenic mice also resulted in elimination of most of the lactotrophsH,~ z. However, a small portion of the lactotrophs escaped ablationS1. Expression of a prolactinthymidine kinase gene did not result in ablation~ 2. These observations support the scheme of lineal relationship between somatotrophs and lactotrophs outlined in Fig. 1, and suggest that the majority of prolactin-expressing cells are post-mitotic somatotrophs. Despite the common precursor, no prolactin expression can be detected until about 10-12 days postnatally in the mouse, while GH expression is first detected on ed 16 (Ref. 13). Thus, the two genes are unlikely to be coordinately activated by a single common factor.