De Coster R, Van Ginckel R, Wouters W, Goeminne N, Vanherck W, Byloos M
Department of Endocrinology and Oncology, Janssen Research Foundation, Beerse, Belgium.
J Enzyme Inhib. 1990;4(2):159-67. doi: 10.3109/14756369009040738.
Some effects of daily oral administration of a new non-steroidal aromatase inhibitor on the pituitary-gonadal and adrenal functions were investigated in female rats. At doses of 1 mg/kg twice daily or higher, R 76713 lowered plasma estradiol levels to the range measured after ovariectomy Plasma progesterone levels and uterine weights decreased whilst LH levels increased but to a lesser extent than after ovariectomy. The other hormonal data show that long-term administration of R 76 713 does not modify the gluco- and mineralocorticoid hormone levels even at the highest dose studied (20 mg/kg, 4 h after treatment). Furthermore, both ovariectomy and R 76 713 treatment (1 and 5 mg/kg twice a day) induced almost complete regression of 9,12-dimethyl-1,2-benzanthracene-induced mammary carcinoma in rats. The appearance of new tumors during the treatment period was completely inhibited by R 76 713 whilst multiplicity of the remaining tumors was dramatically reduced.
研究了每日口服一种新型非甾体芳香化酶抑制剂对雌性大鼠垂体-性腺及肾上腺功能的一些影响。以每日两次、每次1mg/kg或更高剂量给药时，R 76713可使血浆雌二醇水平降至卵巢切除术后测得的范围内。血浆孕酮水平和子宫重量降低，而促黄体生成素水平升高，但升高程度低于卵巢切除术后。其他激素数据表明，即使在研究的最高剂量（20mg/kg，治疗后4小时）下，长期给予R 76 713也不会改变糖皮质激素和盐皮质激素水平。此外，卵巢切除术和R 76 713治疗（每日两次，每次1mg/kg和5mg/kg）均可使9,12-二甲基-1,2-苯并蒽诱导的大鼠乳腺癌几乎完全消退。R 76 713完全抑制了治疗期间新肿瘤的出现，同时显著减少了剩余肿瘤的数量。
