DEVELOPMENT-RELATED EFFECTS OF RECOMBINANT ACTIVIN ON STEROID-SYNTHESIS IN RAT GRANULOSA-CELLS
DEVELOPMENT-RELATED EFFECTS OF RECOMBINANT ACTIVIN ON STEROID-SYNTHESIS IN RAT GRANULOSA-CELLS
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DOI：
10.1210/endo-129-6-3388
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发表时间：
1991-12-01
期刊：
影响因子：
4.8
通讯作者：
HILLIER, SG
中科院分区：
文献类型：
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作者：
MIRO, F;SMYTH, CD;HILLIER, SG
激活素在结构上与多肽生长因子相关，如转化生长因子-β，它可能在卵巢中具有旁分泌和/或自分泌功能。我们研究了激活素在体外对颗粒细胞类固醇合成的作用，以及与体内排卵前卵泡发育的关系。雌激素诱导的未成熟雌性大鼠不接受其他处理(未分化颗粒细胞)、绵羊(O)FSH(已分化颗粒细胞)或oFSH加人(H)CG(排卵前颗粒细胞)处理以刺激排卵前卵泡发育。分离颗粒细胞，在有无重组人激活素-A的条件下，用添加1.0mU-M睾酮的无血清培养基加hFSH、hLH、forsklin或8-bromo-cAMP刺激体外合成类固醇。48h后收集培养液，测定雌二醇(芳香酶活性)、孕酮和cAMP。激活素不影响未分化颗粒细胞的基础类固醇合成，但激活素可剂量依赖性地促进FSH诱导的芳香酶活性和孕酮生成，最高可达10倍。激活素对FSH刺激的cAMP生成无明显影响，但可显著促进Forsklin或8-bromo-cAMP诱导的类固醇合成。因此，激活素对类固醇合成的影响包括在cAMP产生远端的亚细胞水平(S)的作用。体内用促性腺激素处理后，颗粒细胞芳香酶活性和体外孕酮产生对激活素的反应不同。激活素可增强基础、促卵泡激素和促黄体生成素刺激的颗粒细胞芳香酶活性。然而，激活素在分化的颗粒细胞培养中促进基础孕酮的产生，而在排卵前的颗粒细胞中它被抑制。此外，激活素的存在抑制了卵泡刺激素或黄体生成素对体外分化和排卵前颗粒细胞孕酮生成的刺激作用。因此，随着卵泡成熟的进行，大鼠颗粒细胞对激活素表现出与发育相关的类固醇合成反应，芳香酶的产生被增强，孕酮的产生被抑制。这些结果进一步表明激活素是卵巢颗粒细胞类固醇合成的局部调节剂，尽管其功能意义尚未确定。
Activin is structurally related to polypeptide growth factors such as transforming-growth factor-beta, which may have paracrine and/or autocrine functions in the ovaries. We have investigated the action of activin on granulosa cell steroidogenesis in vitro in relation to preovulatory follicular development in vivo. Estrogen-primed immature female rats received no other treatment (nondifferentiated granulosa cells), treatment with ovine (o) FSH (differentiated granulosa cells), or treatment with oFSH followed by human (h) CG (preovulatory granulosa cells) to stimulate preovulatory follicular development. Granulosa cells were isolated and cultured in the presence and absence of recombinant human activin-A using serum-free medium supplemented with 1.0-mu-M testosterone as an aromatase substrate and hFSH, hLH, forskolin, or 8-bromo-cAMP to stimulate steroid synthesis in vitro. After 48 h, medium was collected for measurement of estradiol (aromatase activity), progesterone, and cAMP. Basal steroid synthesis in nondifferentiated granulosa cells was unaffected by activin, but both aromatase activity and progesterone production induced by treatment with FSH in vitro were dosedependently enhanced up to 10-fold by the presence of activin. FSH-stimulated cAMP production was not measurably altered by activin; however, steroidogenesis induced by forskolin or 8-bromo-cAMP was significantly enhanced by the factor. Thus the effect of activin on steroidogenesis includes action at a subcellular level(s) distal to the production of cAMP. After gonadotropin treatment in vivo, granulosa cell aromatase activity and progesterone production showed divergent responses to activin in vitro. Basal-, FSH-, and LH-stimulated aromatase activity were all enhanced by activin in cultures of differentiated and preovulatory granulosa cells. However, whereas basal progesterone production was stimulated by activin in cultures of differentiated granulosa cells, in preovulatory granulosa cells it was inhibited. Moreover, in vitro stimulation of progesterone production by treatment of both differentiated and preovulatory granulosa cells with FSH or LH was suppressed by the presence of activin. Thus rat granulosa cells display development-related steroidogenic responses to activin, aromatase production becoming enhanced and progesterone production suppressed as follicular maturation progresses. These results further implicate activin as a local modulator of granulosa cell steroid synthesis in the ovaries, although its functional significance has yet to be established.