Maeda K, Kitawaki J, Yokota K, Noguchi T, Urabe M, Yamamoto T, Honjo H
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.
Nihon Sanka Fujinka Gakkai Zasshi. 1996 Feb;48(2):89-95.
We studied the direct effects of gonadotropin-releasing hormone (GnRH) and its analogue (buserelin) on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in cultured human granulosa cells which were obtained during oocyte retrieval for in vitro fertilization. Aromatase activity was assessed by radioassay with [1beta-3H]androstenedione as the substrate. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Buserelin stimulated aromatase activity and P-450arom at low concentrations (10(-13) - 10(-9)M), but it suppressed these parameters at high concentrations (10(-8) - 10(-7)M). The stimulatory effect increased with time during 12- to 48-h culture and disappeared after 72-h culture. Follicle-stimulating hormone (FSH) (100 ng/ml) stimulated aromatase activity and the P-450arom concentration but, FSH stimulation was suppressed by co-administration of low or high concentrations of buserelin. In contrast GnRH suppressed aromatase activity and P-450arom at all concentrations (10(-12) - 10(-6)M). GnRH also suppressed FSH stimulation of aromatase. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in human preovulatory granulosa cells, buserelin and GnRH modulate aromatase activity by changing the P-450arom concentration.
我们研究了促性腺激素释放激素(GnRH)及其类似物(布舍瑞林)对体外受精取卵时获得的培养人颗粒细胞中芳香化酶活性和芳香化酶细胞色素P-450(P-450arom)浓度的直接影响。以[1β-3H]雄烯二酮为底物,通过放射测定法评估芳香化酶活性。用针对P-450arom的特异性抗体通过酶联免疫吸附测定法测定P-450arom浓度。低浓度(10^(-13)-10^(-9)M)的布舍瑞林刺激芳香化酶活性和P-450arom,但高浓度(10^(-8)-10^(-7)M)时则抑制这些参数。在12至48小时培养期间,刺激作用随时间增加,72小时培养后消失。促卵泡激素(FSH)(100 ng/ml)刺激芳香化酶活性和P-450arom浓度,但低浓度或高浓度布舍瑞林共同给药可抑制FSH刺激。相反,GnRH在所有浓度(10^(-12)-10^(-6)M)下均抑制芳香化酶活性和P-450arom。GnRH还抑制FSH对芳香化酶的刺激。芳香化酶活性与P-450arom浓度相关。这些结果表明,在人排卵前颗粒细胞中,布舍瑞林和GnRH通过改变P-450arom浓度来调节芳香化酶活性。