Sahlin L, Norstedt G, Eriksson H
Division for Reproductive Endocrinology, Karolinska Hospital, Stockholm, Sweden.
J Steroid Biochem Mol Biol. 1994 Oct;51(1-2):57-66. doi: 10.1016/0960-0760(94)90115-5.
For the first time testosterone is shown to be an important regulator of the insulin-like growth factor-I (IGF-I) in the rat uterus under in vivo conditions. In this study the regulation of IGF-I and the estrogen receptor (ER) by gonadal steroids in the uterus and liver of female rats was monitored. The ER level was assayed by hormone binding after treatment with testosterone, 5 alpha-dihydrotestosterone or estradiol and specific mRNA species were analyzed by a solution hybridization/RNase protection assay using 35S-labeled RNA probes. Ovariectomized rats restored uterine weight after treatment with testosterone. Uterine IGF-I mRNA was more than 20-fold higher in testosterone treated rats compared to untreated ovariectomized controls after 48 h treatment. The effects of testosterone on ovariectomized animals was followed in a timecourse study. Testosterone administration increased uterine IGF-I mRNA expression during the first 48 h and the maximally induced level was maintained throughout the duration of the experiment (168 h). Since induction of IGF-I mRNA by estrogen is transient, these data indicate that androgen and estrogen increase IGF-I mRNA by different mechanisms. Regulation of IGF-I mRNA by gonadal steroids was also studied in hypophysectomized animals. The rats were given either testosterone, 5 alpha-dihydrotestosterone or estradiol, and uterine IGF-I mRNA was measured after 1 week of treatment. At this timepoint estrogen treated rats showed levels of IGF-I mRNA not significantly different from those of hypophysectomized controls. In contrast testosterone and 5 alpha-dihydrotestosterone increased the IGF-I mRNA level 30 and 40 times, respectively, relative to hypophysectomized control animals. Since 5 alpha-dihydrotestosterone is not convertable to estrogen, the induction by testosterone was considered to be a true androgenic phenomenon.
首次证明，在体内条件下，睾酮是大鼠子宫中胰岛素样生长因子-I（IGF-I）的重要调节因子。在本研究中，监测了性腺类固醇对雌性大鼠子宫和肝脏中IGF-I和雌激素受体（ER）的调节。在用睾酮、5α-二氢睾酮或雌二醇处理后，通过激素结合测定ER水平，并使用35S标记的RNA探针通过溶液杂交/核糖核酸酶保护试验分析特定的mRNA种类。去卵巢大鼠在接受睾酮治疗后子宫重量恢复。与未处理的去卵巢对照相比，睾酮处理的大鼠在48小时处理后子宫IGF-I mRNA高出20多倍。在一项时间进程研究中跟踪了睾酮对去卵巢动物的影响。在最初的48小时内，给予睾酮会增加子宫IGF-I mRNA的表达，并且在整个实验期间（168小时）维持最大诱导水平。由于雌激素诱导IGF-I mRNA是短暂的，这些数据表明雄激素和雌激素通过不同机制增加IGF-I mRNA。还在垂体切除的动物中研究了性腺类固醇对IGF-I mRNA的调节。给大鼠分别给予睾酮、5α-二氢睾酮或雌二醇，并在治疗1周后测量子宫IGF-I mRNA。在这个时间点，雌激素处理的大鼠显示出的IGF-I mRNA水平与垂体切除对照无显著差异。相比之下，相对于垂体切除对照动物，睾酮和5α-二氢睾酮分别使IGF-I mRNA水平增加了30倍和40倍。由于5α-二氢睾酮不能转化为雌激素，睾酮的诱导被认为是一种真正的雄激素现象。
