Freyschuss B, Sahlin L, Masironi B, Eriksson H
Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden.
J Endocrinol. 1994 Aug;142(2):285-98. doi: 10.1677/joe.0.1420285.
The regulation of the formation of the hepatic oestrogen receptor (ER) in adult female rats was studied by assaying steady state levels of ER and ER messenger RNA under different endocrine conditions. Hypophysectomy (HX) drastically reduced ER levels from 67.5 +/- 7.9 to 8.4 +/- 0.5 (means +/- S.E.M.) fmol/mg cytosolic protein. Continuous infusion of growth hormone (GH) to HX animals tripled ER and doubled ER mRNA levels. Treatment with triiodothyronine (T3) in a high dose (10 micrograms/day) doubled ER mRNA levels. The effects of T3 were dose-dependent, since a lower dose (1 microgram/day) increased neither ER nor ER mRNA levels. ER mRNA concentrations were increased by GH to 481 +/- 44% and by T3 to 372 +/- 35% of HX control levels 4 h after single injections of the hormones in HX animals. The glucocorticoid dexamethasone (DEX) alone increased neither ER nor ER mRNA levels in HX animals. DEX and GH in combination increased ER 5-fold and ER mRNA 2-fold compared with control levels in HX animals, whereas DEX and T3 in combination increased neither ER nor ER mRNA levels. Treatment with prolactin affected neither ER nor ER mRNA levels in HX rats. Insulin-like growth factor I (IGF-I) mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were measured. GAPDH mRNA levels were increased 2.5-fold in HX rats by DEX and T3 in combination and almost 2-fold by DEX and GH in combination. IGF-I mRNA levels in HX rats were increased 4.5-fold by continuous infusion of GH alone, 6-fold by GH and T3 in combination, and 2.5-fold by GH and DEX in combination. These data indicate that both GH and T3 act directly on the liver to increase ER mRNA levels. GH, the most important of these hormones, also acts at the translational and/or post-translational level to increase ER protein levels. DEX treatment suppresses the stimulatory effects of T3, but not of GH.
通过检测不同内分泌条件下肝雌激素受体（ER）及其信使核糖核酸（mRNA）的稳态水平，研究成年雌性大鼠肝ER形成的调节机制。垂体切除（HX）使ER水平从67.5±7.9急剧降至8.4±0.5（均值±标准误）fmol/mg胞质蛋白。持续向HX动物输注生长激素（GH）使ER水平增加两倍，ER mRNA水平增加一倍。高剂量（10μg/天）三碘甲状腺原氨酸（T3）治疗使ER mRNA水平增加一倍。T3的作用呈剂量依赖性，因为较低剂量（1μg/天）既不增加ER水平也不增加ER mRNA水平。在HX动物单次注射激素4小时后，GH使ER mRNA浓度增加到HX对照水平的481±44%，T3使ER mRNA浓度增加到HX对照水平的372±35%。单独使用糖皮质激素地塞米松（DEX）既不增加HX动物的ER水平也不增加ER mRNA水平。与HX动物对照水平相比，DEX与GH联合使用使ER增加5倍，ER mRNA增加2倍，而DEX与T3联合使用既不增加ER水平也不增加ER mRNA水平。催乳素治疗对HX大鼠的ER水平和ER mRNA水平均无影响。检测胰岛素样生长因子I（IGF-I）mRNA和甘油醛-3-磷酸脱氢酶（GAPDH）mRNA水平。DEX与T3联合使用使HX大鼠的GAPDH mRNA水平增加2.5倍，DEX与GH联合使用使GAPDH mRNA水平增加近2倍。单独持续输注GH使HX大鼠的IGF-I mRNA水平增加4.5倍，GH与T3联合使用使IGF-I mRNA水平增加6倍，GH与DEX联合使用使IGF-I mRNA水平增加2.5倍。这些数据表明，GH和T3均直接作用于肝脏以增加ER mRNA水平。这些激素中最重要的GH还在翻译和/或翻译后水平起作用以增加ER蛋白水平。DEX治疗可抑制T3的刺激作用，但不抑制GH的刺激作用。
