TUMOR NECROSIS FACTOR ALPHA INHIBITS FOLLICLE-STIMULATING HORMONE-INDUCED DIFFERENTIATION IN CULTURED RAT GRANULOSA-CELLS
TUMOR NECROSIS FACTOR ALPHA INHIBITS FOLLICLE-STIMULATING HORMONE-INDUCED DIFFERENTIATION IN CULTURED RAT GRANULOSA-CELLS
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DOI：
10.1016/0006-291x(89)92326-7
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发表时间：
1989-09-15
影响因子：
3.1
通讯作者：
BAYARD, F
中科院分区：
文献类型：
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作者：
DARBON, JM;OURY, F;BAYARD, F
我们已经研究了TNF-α的作用。FSH诱导的LH受体表达，cAMP和孕酮的产生在培养的大鼠颗粒细胞。TNF-.alpha. (0.5- 100 ng/ml）以剂量依赖性方式抑制FSH对LH受体形成的刺激作用，IC 50为1 ng/ml，并且50-100 ng/ml TNF-α几乎完全抑制LH受体诱导。TNF-α的抑制作用不是由于细胞数目或活力的变化，而是由于每个细胞的LH受体含量的减少，而结合亲和力没有变化（KD = 0.8 × 10 - 6）。10-10M）。TNF-.alpha.也抑制FSH诱导的cAMP产生，但程度较低，对于100 ng/ml TNF-α最大降低60%。此外，TNF-α。损害由毛喉素、霍乱毒素或8-溴-cAMP诱导的LH受体形成，表明细胞因子也在远离FSH受体和cAMP形成的步骤起作用。最后，TNF-α。显著降低由FSH刺激的孕酮合成，在10 ng/ml TNF-α时和之后降低至不可检测的水平。这些结果提示TNF-α。可能会显著降低颗粒细胞在FSH刺激下的分化能力和在生理性卵巢卵泡成熟过程中对LH的反应能力。TNF-α的这种抗促性腺激素作用对颗粒细胞分化的影响也可能与炎症或感染性疾病等病理生理过程中卵巢功能的改变有关。
We have investigated the effects of TNF-.alpha. on FSH-induced LH receptor expression, cAMP and progesterone production in cultured rat granulosa cells. TNF-.alpha. (0.5 - 100 ng/ml) inhibits the stimulating action of FSH on LH receptor formation in a dose-dependent manner with an IC50 of 1 ng/ml and an almost complete suppression of LH receptor induction for 50-100 ng/ml TNF-.alpha.. The inhibitory effect of TNF-.alpha. is not due to variations in cell number or viability but rather to a reduction of the LH receptor content per cell with no change in binding affinity (KD = 0.8 .times. 10-10M). TNF-.alpha. also inhibits the FSH-induced cAMP production but at a lower extent, with a maximum reduction of 60% for 100 ng/ml TNF-.alpha.. Moreover, TNF-.alpha. impairs the LH receptor formation induced by forskolin, cholera toxin or 8-Bromo-cAMP, indicating that the cytokine also acts at a step distal to FSH receptor and to cAMP formation. Finally, TNF-.alpha. decreases dramatically the progesterone synthesis that is stimulated by FSH, with a reduction to undetectable levels on and after 10 ng/ml TNF-.alpha.. These results suggest tht TNF-.alpha. may drastically reduce the capacity of granulosa cells to differentiate upon FSH stimulation and to respond to LH during the physiological ovarian follicular maturation. Such anti-gonadotropic action of TNF-.alpha. on granulosa cell differentiation may be also relevant to the alteration of ovarian function during physiopathological processes like inflammatory or infection diseases.