Aguilar R C, Fernandez H N, Dellacha J M, Calandra R S, Bartke A, Ghosh P K, Turyn D
Instituto de Quimica y Fisicoquimica Biologicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Buenos Aires, Argentina.
Transgenic Res. 1992 Sep;1(5):221-7. doi: 10.1007/BF02524752.
The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.
在携带与人金属硫蛋白-I(MT)或磷酸烯醇丙酮酸羧激酶启动子/调节因子(PEPCK)融合的人生长激素(hGH)或牛生长激素(bGH)基因的转基因小鼠的肝脏微粒体制剂中,研究了生长激素受体和催乳激素受体。特异性研究表明,与正常小鼠相似,转基因动物的肝脏微粒体具有生长激素受体和催乳激素结合位点的混合群体。在两性转基因动物中,生长激素受体的结合能力显著增加,而亲和力没有相应变化。MT-hGH杂交基因的表达与生长激素受体的诱导有关,其诱导程度约为表达MT-bGH杂交基因的动物的两倍。与各自的正常对照相比,转基因雌性小鼠肝脏微粒体中催乳激素受体的结合能力(通过使用标记的绵羊催乳素来定量)增加了2-3倍,转基因雄性小鼠中增加了约10倍。我们得出结论,终身过量的生长激素会上调肝脏生长激素和催乳激素受体,并且生长激素的催乳活性对于转基因小鼠肝脏中催乳激素受体的诱导不是必需的。