Wang H, Isaksson E, Von Schoultz B, Cline J M, Sahlin L
Division for Reproductive Endocrinology, Department of Woman and Child Health, Karolinska Hospital, 17176 Stockholm, Sweden.
J Endocrinol. 2002 Dec;175(3):673-81. doi: 10.1677/joe.0.1750673.
The effects of oestrogen are mediated by two specific intracellular receptors, oestrogen receptors (ER) alpha and beta, which function as ligand-activated transcriptional regulators. Ovariectomized macaques (Macaca fascicularis) were used to study the regulation of ERalpha and ERbeta in the endometrium by immunohistochemistry and in situ hybridization after long-term hormone treatment. Animals were treated continuously for 35 Months with either conjugated equine oestrogen (CEE), medroxyprogesterone acetate (MPA), combined CEE/MPA, or tamoxifen (TAM). Treatment with CEE/MPA down-regulated ERalpha in the superficial glands. In the superficial stroma the ERalpha level was lower in the CEE/MPA group than in the CEE and MPA groups. ERbeta immunostaining was faint with minor variation in response to treatment, but increased in the superficial stroma after MPA treatment. The ratio of ERbeta/ERalpha increased in superficial stroma and gland after CEE/MPA treatment, and also in stroma after MPA and TAM. Cystic endometrial hyperplasia was observed in TAM-treated animals, in combination with a high level of ERalpha protein expression. The present data show that long-term hormone treatment affects the ERalpha and ERbeta protein levels in the endometrium. The balance between ERalpha and ERbeta seems to be important for the proliferative response to oestrogen.
雌激素的作用由两种特定的细胞内受体介导，即雌激素受体（ER）α和β，它们作为配体激活的转录调节因子发挥作用。采用去卵巢猕猴（食蟹猴），通过免疫组织化学和原位杂交技术，研究长期激素治疗后子宫内膜中ERα和ERβ的调节情况。动物连续35个月接受共轭马雌激素（CEE）、醋酸甲羟孕酮（MPA）、联合CEE/MPA或他莫昔芬（TAM）治疗。CEE/MPA治疗下调了浅表腺体中的ERα。在浅表基质中，CEE/MPA组的ERα水平低于CEE组和MPA组。ERβ免疫染色较弱，对治疗的反应变化较小，但MPA治疗后浅表基质中的ERβ增加。CEE/MPA治疗后，浅表基质和腺体中ERβ/ERα的比值增加，MPA和TAM治疗后的基质中该比值也增加。在接受TAM治疗的动物中观察到囊性子宫内膜增生，同时伴有高水平的ERα蛋白表达。目前的数据表明，长期激素治疗会影响子宫内膜中ERα和ERβ的蛋白水平。ERα和ERβ之间的平衡似乎对雌激素的增殖反应很重要。
