Cecim M, Alvarez-Sanz M, Van de Kar L, Milton S, Bartke A
Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901-6512, USA.
Transgenic Res. 1996 May;5(3):187-92. doi: 10.1007/BF01969708.
Previous work from our laboratory provided evidence for increased plasma corticosterone levels in mice transgenic for human and bovine growth hormone (GH). Corticosterone was elevated in both sexes, under both basal and ether-induced stress conditions. The objectives of the present study were to investigate the in vitro adrenal sensitivity to ACTH, GH and/or IGF-I in normal and bGH transgenic mice, to examine plasma corticosterone levels at different times of the day, and to determine plasma levels of ACTH in these animals. For the measurement of plasma corticosterone and ACTH levels, transgenic and normal siblings were housed 2 per cage and decapitated simultaneously within 20 seconds of the first disturbance of the cage. The corticosterone production by in vitro adrenal incubations did not differ between adrenals from normal and transgenic mice at the basal level or in the presence of different doses of ACTH. Growth hormone or IGF-I did not have any effect on corticosterone production in vitro when given alone, and did not modify the effects of ACTH on the accumulation of corticosterone production in vitro when alone, and did not modify the effects of ACTH on the accumulation of corticosterone in the media. Plasma corticosterone concentrations were higher in transgenic than in normal animals in both morning and evening. Plasma concentrations of ACTH in animals killed in the morning were sharply increased in transgenic males as compared with their normal siblings. The results indicate that increased circulating levels of corticosterone in transgenic mice are not due to a potentiation of ACTH actions by GH or IGF-I, but rather to a chronic increase in plasma ACTH levels. The increase in ACTH is presumably a reflection of GH actions in the hypothalamic-pituitary system.
我们实验室之前的研究为转人及牛生长激素（GH）基因小鼠血浆皮质酮水平升高提供了证据。在基础状态和乙醚诱导的应激条件下，雌雄小鼠的皮质酮水平均升高。本研究的目的是调查正常和bGH转基因小鼠体外肾上腺对促肾上腺皮质激素（ACTH）、GH和/或胰岛素样生长因子-I（IGF-I）的敏感性，检测一天中不同时间的血浆皮质酮水平，并测定这些动物的血浆ACTH水平。为了测量血浆皮质酮和ACTH水平，将转基因小鼠和正常同窝小鼠每笼饲养2只，并在首次扰动笼子后20秒内同时断头。在基础水平或存在不同剂量ACTH的情况下，正常小鼠和转基因小鼠肾上腺体外培养产生的皮质酮没有差异。单独给予生长激素或IGF-I时，对体外皮质酮产生没有任何影响，单独给予时也不会改变ACTH对体外皮质酮产生积累的影响，也不会改变ACTH对培养基中皮质酮积累的影响。转基因动物早晨和晚上的血浆皮质酮浓度均高于正常动物。与正常同窝小鼠相比，转基因雄性小鼠早晨处死时的血浆ACTH浓度急剧升高。结果表明，转基因小鼠循环中皮质酮水平升高不是由于GH或IGF-I增强了ACTH的作用，而是由于血浆ACTH水平的慢性升高。ACTH的升高可能反映了下丘脑-垂体系统中GH的作用。
