Noguchi S, Ohba Y, Oka T
Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1991 Apr;128(4):2141-8. doi: 10.1210/endo-128-4-2141.
The effects of testosterone on the levels of epidermal growth factor receptor (EGFR) in mouse liver were studied. Orchiectomy resulted in 39% and 41% reductions in the levels of EGFR mRNA and EGF binding, respectively, within 2 weeks. Treatment of orchiectomized mice with a sc injection of testosterone propionate (TP; 100 micrograms/mouse.day) for 1 week restored these values to normal male levels. The hepatic levels of EGFR mRNA and EGF binding in females were 37% and 36% of those in males, respectively, and were not affected by ovariectomy, whereas treatment of females with TP (100 micrograms/mouse.day) increased EGFR to normal male levels within 1 week. On the other hand, neither orchiectomy nor androgen treatment affected levels of mRNAs for EGFR in the kidney or mRNAs for the structural protein beta-actin in the liver. To examine whether testosterone directly increased EGFR levels in the liver, TP (1.0 mg) pellets were implanted into the spleen of orchiectomized mice, so that testosterone released from the pellets reached the liver through the portal vein but did not enter the systemic circulation due to rapid clearance by the liver. The heptic levels of EGFR mRNA and EGF binding in orchiectomized mice were restored to normal male levels by intrasplenic implantation of TP (1.0 mg) pellets. This treatment also increased the hepatic levels of EGFR mRNA and EGF binding in female mice by 61% and 68%, respectively. In addition, sialoadenectomy, which reduced plasma EGF, as well as EGF antiserum treatment did not affect the androgen-dependent increase in EGFR levels in the liver, suggesting that endogenous EGF is not involved in the androgenic regulation of hepatic EGFR levels. These results suggest that hepatic EGFR levels are at least in part regulated at a pretranslational level by direct effects of androgens on the liver.
研究了睾酮对小鼠肝脏中表皮生长因子受体（EGFR）水平的影响。去势导致在2周内EGFR mRNA水平和EGF结合水平分别降低39%和41%。对去势小鼠皮下注射丙酸睾酮（TP；100微克/小鼠·天）治疗1周，可使这些值恢复到正常雄性水平。雌性小鼠肝脏中EGFR mRNA水平和EGF结合水平分别为雄性小鼠的37%和36%，且不受卵巢切除的影响，而用TP（100微克/小鼠·天）治疗雌性小鼠1周内可使EGFR增加到正常雄性水平。另一方面，去势和雄激素治疗均不影响肾脏中EGFR的mRNA水平或肝脏中结构蛋白β-肌动蛋白的mRNA水平。为了研究睾酮是否直接增加肝脏中EGFR的水平，将TP（1.0毫克）药丸植入去势小鼠的脾脏，使得从药丸释放的睾酮通过门静脉到达肝脏，但由于肝脏的快速清除而不进入体循环。通过脾脏内植入TP（1.0毫克）药丸，去势小鼠肝脏中EGFR mRNA水平和EGF结合水平恢复到正常雄性水平。这种治疗还分别使雌性小鼠肝脏中EGFR mRNA水平和EGF结合水平增加了61%和68%。此外，减少血浆EGF的涎腺切除术以及EGF抗血清治疗均不影响肝脏中EGFR水平的雄激素依赖性增加，这表明内源性EGF不参与肝脏EGFR水平的雄激素调节。这些结果表明，肝脏中EGFR水平至少部分地在转录前水平受到雄激素对肝脏的直接作用的调节。
