Chandrashekar V, Bartke A, Wagner T E
Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901-6512.
Endocrinology. 1992 Apr;130(4):1802-8. doi: 10.1210/endo.130.4.1547710.
Adult female transgenic mice expressing the human GH (hGH) gene with mouse metallothionein-I promoter are sterile. To evaluate the hypothalamic-pituitary function in these animals, adult female transgenic mice and nontransgenic normal littermates were ovariectomized. On days 7 and 8 after ovariectomy, mice were injected with either oil or primed with 0.5 micrograms estradiol benzoate (EB) in oil, 24 h later treated with 10 micrograms EB/100 g body wt and a day later bled for measurements of FSH, LH, and PRL levels. Plasma gonadotropin and PRL levels were also measured in ovary-intact transgenic and normal siblings at estrus. Additional ovariectomized EB-treated transgenic mice and normal siblings were injected with either saline or GnRH in saline (1 ng/g body wt) and were bled 15 min later for determination of circulating hormone levels. At estrus, in transgenic mice, circulating FSH and PRL levels were significantly lower (FSH:P less than 0.001; PRL:P less than 0.025), but plasma LH concentrations were higher (P less than 0.001) than those in nontransgenic mice. As expected, ovariectomy significantly increased (P less than 0.001) circulating FSH and LH levels in both groups of mice relative to ovary-intact animals, but the increase in plasma LH levels was attenuated in transgenic mice. The suppressive effect of estrogen on circulating FSH and LH levels were similar in transgenic and nontransgenic mice. Treatment with GnRH significantly increased plasma FSH and LH levels in both transgenic and normal mice. However, the plasma FSH and LH responses to GnRH administration were significantly reduced (P less than 0.001) in transgenic mice. The results of these studies indicate that adult female transgenic mice expressing the hGH gene are hypoprolactinemic. Yet due to PRL-like activity of hGH, the gonadotropin secretion is altered. Thus, endogenously secreted hGH modulates the hypothalamic-pituitary function of adult female transgenic mice bearing the hGH gene.
表达带有小鼠金属硫蛋白-I启动子的人生长激素（hGH）基因的成年雌性转基因小鼠不育。为了评估这些动物的下丘脑-垂体功能，对成年雌性转基因小鼠和非转基因正常同窝仔鼠进行了卵巢切除术。在卵巢切除术后第7天和第8天，给小鼠注射油剂，或者先用0.5微克溶于油剂中的苯甲酸雌二醇（EB）进行预处理，24小时后用10微克EB/100克体重进行处理，一天后采血以测定FSH、LH和PRL水平。还在处于发情期的卵巢完整的转基因和正常同窝仔鼠中测量了血浆促性腺激素和PRL水平。另外，对经EB处理的卵巢切除的转基因小鼠和正常同窝仔鼠注射生理盐水或溶于生理盐水的GnRH（1纳克/克体重），15分钟后采血以测定循环激素水平。在发情期，转基因小鼠的循环FSH和PRL水平显著较低（FSH：P<0.001；PRL：P<0.025），但血浆LH浓度较高（P<0.001），高于非转基因小鼠。正如预期的那样，相对于卵巢完整的动物，卵巢切除术使两组小鼠的循环FSH和LH水平显著升高（P<0.001），但转基因小鼠血浆LH水平的升高有所减弱。雌激素对循环FSH和LH水平的抑制作用在转基因和非转基因小鼠中相似。用GnRH处理使转基因和正常小鼠的血浆FSH和LH水平均显著升高。然而，转基因小鼠中血浆FSH和LH对GnRH给药的反应显著降低（P<0.001）。这些研究结果表明，表达hGH基因的成年雌性转基因小鼠催乳素分泌不足。然而，由于hGH的催乳素样活性，促性腺激素分泌发生改变。因此，内源性分泌的hGH调节携带hGH基因的成年雌性转基因小鼠的下丘脑-垂体功能。
