Bengtsson M, Dong Y, Mattison D R, Rydstrom J
Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Chem Biol Interact. 1987;63(1):15-27. doi: 10.1016/0009-2797(87)90101-3.
The mechanisms of regulation of ovarian 7,12-dimethylbenz[a]anthracene (DMBA) hydroxylase were investigated with respect to hormonal requirements and effects of the antiestrogen tamoxifen and known inducers of cytochrome P-450. The DMBA hydroxylase is increased endogenously about 3-fold in the proestrus phase as compared to the metestrus/diestrus phases (M. Bengtsson and J. Rydstrom, Science, 219 (1983) 1437-1438). A similar effect was caused by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) whereas pregnant mare's serum gonadotropin (PMSG) brought about a 3-7-fold increase, suggesting that the estrus cycle-dependence of the DMBA hydroxylase was due directly or indirectly to gonadotropins. In contrast, differentiation of granulosa/theca cells to corpus luteum cells after ovulation, caused by administration of human chorionic gonadotropin (hCG), led to a marked decrease in activity. The activity was not specific for DMBA since substitution of this hydrocarbon for benzo[a]pyrene (BP) as substrate gave similar results. A possible role of estrogens in this context was investigated by the administration of tamoxifen simultaneous with gonadotropin treatment, which caused a partial inhibition of the hydroxylase activity. Both estradiol and 3-methyl-cholanthrene (MC) increased DMBA hydroxylase but the effects of these agents were not additive. In contrast, the effects of estradiol and MC were partially additive to that of gonadotropin. On the basis of these results, it is proposed that the rat ovary contains one or several aryl hydrocarbon hydroxylases located in the granulosa/theca cells which are regulated by estrogens, MC and beta-naphthoflavone (BNF) and that the role of gonadotropins is to proliferate granulosa/theca cells.
针对激素需求、抗雌激素他莫昔芬以及已知细胞色素P - 450诱导剂的影响，对卵巢7,12 - 二甲基苯并[a]蒽（DMBA）羟化酶的调节机制进行了研究。与动情后期/间情期相比，DMBA羟化酶在动情前期内源性增加约3倍（M. Bengtsson和J. Rydstrom，《科学》，219 (1983) 1437 - 1438）。促性腺激素促卵泡激素（FSH）和促黄体生成素（LH）产生了类似的效果，而孕马血清促性腺激素（PMSG）则使该酶增加3 - 7倍，这表明DMBA羟化酶对发情周期的依赖性直接或间接归因于促性腺激素。相反，人绒毛膜促性腺激素（hCG）给药导致排卵后颗粒细胞/卵泡膜细胞分化为黄体细胞，进而使酶活性显著降低。该活性对DMBA不具有特异性，因为用苯并[a]芘（BP）替代这种烃作为底物时也得到了类似结果。通过在促性腺激素治疗的同时给予他莫昔芬，研究了雌激素在这一过程中的可能作用，结果导致羟化酶活性部分受到抑制。雌二醇和3 - 甲基胆蒽（MC）均能增加DMBA羟化酶活性，但这些试剂的作用并非相加性的。相反，雌二醇和MC的作用与促性腺激素的作用部分具有相加性。基于这些结果，有人提出大鼠卵巢的颗粒细胞/卵泡膜细胞中含有一种或几种芳烃羟化酶，它们受雌激素、MC和β - 萘黄酮（BNF）调节，且促性腺激素的作用是使颗粒细胞/卵泡膜细胞增殖。
