Progestin-dependent effect of forskolin on human endometrial aromatase activity.

Progestin-dependent effect of forskolin on human endometrial aromatase activity.
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毛喉素对人子宫内膜芳香酶活性的孕激素依赖性影响。

DOI:
10.1093/oxfordjournals.humrep.a136553
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发表时间:
1987
期刊:
Human reproduction (Oxford, England)
影响因子:
--
通讯作者:
Tseng,A
Tseng,A
中科院分区:
--
文献类型:
--
作者:
Tseng,L;Malbon,CC;Lane,B;Kaplan,C;Mazella,J;Dahler,H;Tseng,A

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我们以前已经证明,芳香化酶的活性在人子宫内膜间质细胞的刺激,由rexestin和增强雌激素。在这项研究中,我们已经调查了毛喉素(飞度),一个代理人,刺激哺乳动物细胞中的腺苷酸环化酶敏感,对细胞内cAMP含量和芳香化酶活性在子宫内膜间质细胞在原代培养的效果。从增殖和分泌型卵巢中分离基质细胞,并分别在营养培养基或补充有醋酸甲羟孕酮(MPA)、雌二醇(E2)和Fk的培养基中单独或组合培养。Fk作用后,基质细胞内cAMP含量增加。用单独的FK或FK和MPA处理1-3天的基质细胞维持升高的细胞内cAMP含量,但90%的这种核苷酸被释放到培养基中。芳香化酶活性不受影响,或增加到5倍以上的控制由单独的FK。毛喉素对芳香化酶活性产生协同作用,在存在下的residestin或residestin和雌二醇。依次孵育的基质细胞与MPA,然后Fk表明,额外的增加芳香化酶活性引起的Fk发生后24小时的孵育。这些结果表明,在孕激素调节的基质细胞中,细胞内cAMP对芳香化酶活性发挥刺激作用。我们还调查了子宫内膜芳香化酶活性是否在体内的变化,在生殖周期中,通过测量子宫内膜标本中的活动,从妇女在其生育年龄。孕早期增生期、分泌期子宫内膜和蜕膜芳香化酶活性(fmol/h × mg蛋白)的平均值分别为1.6 ± 1.0(mean ± SD,n = 10)、3.0 ± 3.4(n = 13)和1500 ± 900(n = 20)。这些结果表明,子宫内膜芳香化酶活性的刺激发生在生理条件下受孕后。这些观察结果为研究cAMP在子宫内膜细胞中依赖类固醇激素的调节过程中的作用提供了可能性
We have previously demonstrated that the aromatase activity in human endometrial stromal cells is stimulated by progestin and enhanced by oestrogen. In this study, we have investigated the effect of forskolin (Fit), an agent that stimulates the hormone-sensitive adenylate cydase in mammalian cells, on the intracellular cAMP content and aromatase activity in endometrial stromal cells in primary culture. Stromal cells were isolated from proliferative and secretory endometria and were individually cultured in nutrient medium or medium supplemented with medroxyprogesterone acetate (MPA), oestradiol (E2) and Fk, separately or in combination. The intracellular cAMP content of stromal cells was increased after incubation with Fk. Stromal cells treated with Fk alone or FK and MPA for 1-3 days sustained the elevated intracellular cAMP content but 90% of this nuckotide was released to the medium. Aromatase activity was either not affected or was increased up to 5-fold over the control by Fk alone. Forskolin exerted a synergistic effect upon aromatase activity in the presence of progestin or progestin and oestradiol. Sequential incubation of the stromal cells with MPA and then Fk indicated that the additional increase in aromatase activity caused by Fk occurred after 24 h of incubation. These results demonstrate that intracellular cAMP exerts a stimulatory effect on aromatase activity in progestin-conditioned stromal cells. We also investigated whether the endometrial aromatase activity changes in vivo during the reproductive cycle by measuring the activities in endometrial specimens obtained from women during their reproductive age. The mean values of aromatase activities (fmol/h x mg protein) in proliferative, secretory endometria and decidua from first trimester of the gestation were 1.6 ± 1.0 (mean ± SD, n = 10), 3.0 ± 3.4 (n = 13) and 1500 ± 900 (n = 20), respectively. These results indicate that stimulation of endometrial aromatase activity occurs after conception under physiological conditions. These observations open possibilities for the study of the role of cAMP in the expression of regulatory processes dependent upon steroid hormones in endometrial cells