Tang K, Bartke A, Gardiner C S, Wagner T E, Yun J S
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901.
Biol Reprod. 1993 Aug;49(2):346-53. doi: 10.1095/biolreprod49.2.346.
Expression of the mouse metallothionein-I (MT) promoter/bovine growth hormone (bGH) or the phosphoenolpyruvate carboxykinase (Pepck) promoter/bGH fusion genes in male transgenic mice is associated with alternations in adenohypophyseal function and fertility. To determine the effects of these gene constructs on gonadotropin synthesis and secretion, we have examined basal and GnRH-stimulated LH and FSH release in vitro using static incubations and perifusions of the pituitary; we have also examined pituitary content of LH, FSH, LH beta mRNA, and FSH beta mRNA in MT/bGH and Pepck/bGH transgenic mice as well as in normal mice. In addition, we have measured LH and FSH release from normal pituitaries transplanted under the kidney capsules of Pepck/bGH transgenic or normal mice. We found that in Pepck/bGH transgenic mice, pituitary contents of FSH and FSH beta mRNA were reduced, while FSH release in vitro in pituitary incubations and perifusions was increased. Steady-state levels of LH beta mRNA as well as LH responses to GnRH in perifusions were reduced; LH release in incubations and pituitary LH content were not changed; and basal LH secretion in perifusions was increased. In MT/bGH transgenic mice, in which peripheral bGH levels are much lower than in Pepck/bGH mice, similar trends were observed, but most of the apparent differences between transgenic and normal animals were not statistically significant. When normal pituitaries were transplanted under the kidney capsules of Pepck/bGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the response to GnRH stimulation was lost.(ABSTRACT TRUNCATED AT 250 WORDS)
小鼠金属硫蛋白-I(MT)启动子/牛生长激素(bGH)或磷酸烯醇式丙酮酸羧激酶(Pepck)启动子/bGH融合基因在雄性转基因小鼠中的表达与腺垂体功能和生育能力的改变有关。为了确定这些基因构建体对促性腺激素合成和分泌的影响,我们使用垂体的静态孵育和灌流法检测了体外基础状态下以及GnRH刺激后的LH和FSH释放;我们还检测了MT/bGH和Pepck/bGH转基因小鼠以及正常小鼠垂体中LH、FSH、LHβmRNA和FSHβmRNA的含量。此外,我们测量了移植到Pepck/bGH转基因小鼠或正常小鼠肾囊下的正常垂体释放的LH和FSH。我们发现,在Pepck/bGH转基因小鼠中,垂体FSH和FSHβmRNA的含量降低,而垂体孵育和灌流时体外FSH释放增加。灌流中LHβmRNA的稳态水平以及LH对GnRH的反应降低;孵育时LH释放和垂体LH含量未改变;灌流中基础LH分泌增加。在MT/bGH转基因小鼠中,外周bGH水平远低于Pepck/bGH小鼠,观察到类似趋势,但转基因动物与正常动物之间的大多数明显差异无统计学意义。当将正常垂体移植到Pepck/bGH转基因小鼠的肾囊下时,LH和FSH分泌的预期减少减弱,对GnRH刺激的反应丧失。(摘要截短于250词)