Effect of in vivo gonadotropin treatment on the ability of progesterone, estrogen, and cyclic adenosine 5'-monophosphate to inhibit insulin-dependent granulosa cell mitosis in vitro.

Effect of in vivo gonadotropin treatment on the ability of progesterone, estrogen, and cyclic adenosine 5'-monophosphate to inhibit insulin-dependent granulosa cell mitosis in vitro.
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体内促性腺激素治疗对孕酮、雌激素和环腺苷 5-单磷酸体外抑制胰岛素依赖性颗粒细胞有丝分裂的能力的影响。

DOI:
10.1095/biolreprod53.3.664
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发表时间:
1995
影响因子:
3.6
通讯作者:
Peluso,JJ
Peluso,JJ
中科院分区:
生物学2区
文献类型:
--
作者:
Luciano,AM;Peluso,JJ

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检测孕酮(P4)、雌二醇-17 β(E2)和8-溴(br)-cAMP抑制小颗粒细胞(GC)进行胰岛素依赖性有丝分裂的能力。从未成熟和eCG-致敏的大鼠中分离小GC,并通过Percoll分级分离。用胰岛素、类固醇、类固醇受体拮抗剂和8-br-cAMP的各种组合培养小GC 24小时。培养前后计数GC数。小GC增殖表示为相对于初始值的百分比增加。P4抑制了从未成熟和hCG致敏大鼠中分离的小GC的胰岛素依赖性有丝分裂。P4的作用呈剂量依赖性、类固醇特异性,可被孕酮拮抗剂RU 486逆转。E2抑制未成熟大鼠小GC的胰岛素依赖性有丝分裂,但不抑制hCG致敏大鼠的有丝分裂。E2的作用呈剂量依赖性,可被雌激素拮抗剂他莫昔芬抑制。另外还进行了一些研究,在P4和E2及其各自的拮抗剂存在下,将未成熟大鼠的小GC与胰岛素一起培养。在P4和E2存在的情况下,这两种拮抗剂都是胰岛素诱导GC有丝分裂所必需的。此外,P4抑制胰岛素依赖性有丝分裂的能力降低,如果它不存在于第一个6小时的文化。相反,E2可以在胰岛素暴露后12小时加入,并且仍然完全阻止GC有丝分裂。8-br-cAMP也阻止胰岛素依赖性GC增殖。8-br-cAMP的作用不能被氨鲁米特或RU 486逆转。这表明8-br-cAMP不会通过增加类固醇合成来阻断有丝分裂。综上所述,这些数据表明,胰岛素依赖性有丝分裂的小GC从未成年大鼠分离的负调控P4,E2,和8-br-cAMP。这些调节剂中的每一种似乎通过不同的细胞途径介导其抗有丝分裂作用。此外,在体内用eCG处理可诱导小GC内的变化,导致E2的抗有丝分裂作用丧失。
The ability of progesterone (P4),s tradiol-17β (E2), and 8-bromo (br)-cAMP to inhibit small granulosa cells (GCs) from undergoing insulin-dependent mitosis was examined. Small GCs were isolated from immature and eCG-primed rats and separated by Percoll fractionation. Small GCs were cultured for 24 h with various combinations of insulin, steroids, steroid receptor antagonists, and 8-br-cAMP. Before and after culture, the number of GCs was counted. Small GC proliferation was expressed as a percentage increase over the initial value. P4inhibited insulin-dependent mitosis of small GCs isolated from both immature and eCG-primed rats. The effects of P4were dosedependent, steroid-specific, and reversed by the progesterone antagonist RU486. E2inhibited insulin-dependent mitosis of small GCs isolated from immature but not eCG-primed rats. The action of E2was dose-dependent and inhibited by the estrogen antagonisttamoxifen. Additional studies were conducted in which small GCs from immature rats were cultured with insulin in the presence of both P4and E2and their respective antagonist. Both antagonists were required for insulin to induce GC mitosis in the presence of P4and E2. Further, the ability of P4to suppress insulin-dependent mitosis was reduced if it was not present during the first 6 h of culture. In contrast, E2could be added up to 12 h after insulin exposure and still completely prevent GC mitosis. 8-br-cAMP also prevented insulin-dependent GC proliferation. The actions of 8-br-cAMP could not be reversed by aminoglutethimide or RU486. This indicates that 8-br-cAMP does not block mitosis by increasing steroid synthesis. Taken together, these data demonstrate that insulin-dependent mitosis of small GCs isolated from immature rats is negatively regulated by P4, E2, and 8-br-cAMP. Each of these regulators appears to mediate their antimitotic action through different cellular pathways. Further, in vivo treatmentwith eCG induces changes within small GCs that result in the loss of E2′s antimitogenic action.
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发表时间: 1991-07-01
影响因子: --
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