Fernández L, Boada L D, Luzardo O P, Zumbado M, Díaz-Chico J C, Díaz-Chico B N, Chirino R
Departamentos de Endocrinología Celular y Molecular, Universidad de Las Palmas de Gran Canaria, Canary Islands, Spain.
J Pharmacol Exp Ther. 1994 Sep;270(3):1121-6.
The present work focuses on the interaction of 17 alpha-ethinyl estrogen derivatives with the [3H]dexamethasone ([3H]DEX) binding site from male rat liver microsomes and the induction of this site by the in vivo administration of natural and synthetic estrogens. [3H]DEX binds to a single-saturating binding site (Kd = 100 nM; maximal binding = 13 pmol/mg of protein) in the liver microsomes. In competition experiments, ethinylestradiol (EE2) and mestranol were able to inhibit [3H]DEX binding to microsomes, whereas natural estrogens, tamoxifen or estrogen sulfates were ineffective. Saturation analysis performed by incubating [3H]EE2 with liver microsomes revealed the existence of a low-affinity (Kd = 280 +/- 30 nM) and high capacity (maximal binding = 16 +/- 2 pmol/mg of protein) binding site. Saturation, competition and dissociation experiments suggest that [3H]DEX and [3H]EE2 interact with the same microsomal entity. Synthetic and natural estrogens increased the hepatic expression of the [3H]DEX binding site in immature, hypothyroid and hypophysectomized male rats. This induction required at least 2 days of treatment, and could only be achieved by pharmacological doses of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究聚焦于17α-乙炔基雌激素衍生物与雄性大鼠肝脏微粒体中[3H]地塞米松（[3H]DEX）结合位点的相互作用，以及天然和合成雌激素体内给药对该位点的诱导作用。[3H]DEX与肝脏微粒体中的单一饱和结合位点结合（解离常数Kd = 100 nM；最大结合量 = 13 pmol/mg蛋白质）。在竞争实验中，乙炔雌二醇（EE2）和炔雌醇能够抑制[3H]DEX与微粒体的结合，而天然雌激素、他莫昔芬或雌激素硫酸盐则无效。用[3H]EE2与肝脏微粒体孵育进行的饱和分析显示存在一个低亲和力（Kd = 280±30 nM）和高容量（最大结合量 = 16±2 pmol/mg蛋白质）的结合位点。饱和、竞争和解离实验表明，[3H]DEX和[3H]EE2与同一微粒体实体相互作用。合成和天然雌激素可增加未成熟、甲状腺功能减退和垂体切除雄性大鼠肝脏中[3H]DEX结合位点的表达。这种诱导至少需要2天的治疗，并且只能通过药理剂量的雌激素来实现。（摘要截短于250字）
