PARADOXICAL EFFECT OF A GnRH AGONIST ON STEROIDOGENESIS IN CULTURED MONKEY GRANULOSA CELLS

In this study we demonstrate: (i) The GnRH agonist exerts a direct dose-dependet stimulative effect on the aromatase activity and progesterone production in cultured monkey granulosa cells; (ii)the stimulative effect on steroidogenesis can be completely blocked by concomitant treatment with a GnRH antagonist, suggesting that the actions of GnRH are mediated through stringent stereospecific recongnition sites; (iii) in addition to the stimulative effect, the GnRH agonist in the presence of gonadotropins also exerts an inhibitory effect, even though the peptide by itself is more effective in the stimulation of steroidogenesis, and the stimulation of gonadotropin on steroidogenesis could be gradually restored by decreasing the concentration of the GnRH agonist in the culture; and (iv) paradoxical effect can also be observed in the presence of cAMP-inducing agents, suggesting that the inhibitory action of the peptide on gonadotropin-induced steroidogenesis is localized at a step distal to the stringent reco     

GnRHa对恒河猴颗粒细胞离体下甾体激素形成的双向作用

实验证明:(1)促性腺激素释放激素类似物(GnRHa)刺激猴颗粒细胞芳香化酶活性和孕酮产生,并与剂量有直接关系;(2)GnRH拮抗物能完全阻断GnRHa的作用,表明GnRHa是通过颗粒细胞表面受体对其甾体形成起作用的;(3)除刺激作用外,GnRHa与促性腺激素一起则抑制雌激素和孕酮的产生;降低GnRHa的含量可逐渐恢复促性腺激素对甾体形成的刺激作用;(4)GnRHa对颗粒细胞的双向作用在cAMP诱导剂存在下也可观察到,这说明GnRHa抑制促性腺激素诱导甾体激素的形成是发生在受体结合以后的信息传递系统的某个部位上。     

A FACTOR FROM GRANULOSA CELLS CAN STIMULATE OOCYTE TISSUE PLASMINOGEN ACTIVATOR ACTIVITY

Several studies indicate that substances synthesized by granulosa cells are capableof regulating oocyte activity. We have studied the effect of factors synthesized by gran-ulosa cells on tPA activity of denuded oocytes using a co- culture system. The resultsshow that an FSH- dependent factor(s) synthesized by granulosa cells (but not by theca-interstitial cells) is capable of stimulating tPA activity of denuded oocytes. This findingis important for understanding hormonal regulation of oocyte tPA activity by mediatorssynthesized in granulosa cells.     

A FACTOR(S) PRODUCED BY SERTOLI CELLS STIMULATES ANDROGEN BIOSYNTHESIS BY LEYDIG CELLS IN NEONATAL RATS

Using a coculture system, we have studied the local action of Sertoli cells on Leydig cell function. The results show that (ⅰ) both LH and FSH have equal potency to stimulate testosterone biosynthesis by fetal and neonatal testicular cells in an age-dependent manner, the maximum stimulation is observed between D_3 and D_5. (ⅱ) An FSH-dependent factor(s) secreted by Sertoli cells increases the basal and/or LH-stimulated Leydig cell androgen production. (ⅲ) The Sertoli cell-stimulating factor(s) is not a steroid or other small molecule, but a heat-labile peptide.     

颗粒细胞分泌一种刺激卵母细胞组织型纤蛋白溶酶原激活因子的物质

本工作用颗粒细胞或颗粒细胞培液与卵母细胞一起培养的方法研究了颗粒细胞因子对卵母细胞纤蛋白溶酶原激活因子的影响。结果表明,在FSH作用下,颗粒细胞分泌一种(些)刺激卵母细胞tPA活性的因子。这一发现对了解激素通过颗粒细胞合成中间因子调节卵母细胞tPA活性有重要意义。     

INTERACTION AND REGULATION OF PLASMINOGEN ACTIVATORS AND THEIR INHIBITOR IN RAT FOLLICLES DURING PERIOVULATORY PERIODS

Ovarian follicles produce two types of plasminogen activator (tPA and uPA), and their inhibitor(PAI). We have examined the interaction and regulation of these factors in ovarian intact follicles aswell as granulosa and theca-interstitial cells. The results show that only tPA, but not uPA, is regulated bythe gonadotropins and reaches maximum prior to ovulation. PAI is secreted mainly by theca-interstitialcells and is stimulated also by the gonadotropins. The formation of complexes between PA and PAI com-pletely blocks or decreases PA activity. It is suggested that the interaction between plasminogen activatorsand their inhibitor in the follicles may play a very important role in maintaining normal ovarian functionand the machnism of ovulation.     

INDOMETHACIN INHIBITS hCG AND GnRH AGONIST-INDUCED SECRETION OF PLASMINOGEN ACTIVATOR BY GRANULOSA AND THECA INTERSTITIAL CELLS OF HYPOPHYSECTOMIZED RATS

Considerable data have shown that plasminogen activator (PA) may play an important role in the mechanism of ovulation. A recent report argued that PA is not a primary proteoIytic enzyme for follicular rupture because a dose of indomethacin that blocked ovulation did not inhibit ovarian PA content. To further clarify the specific role of PA in the ovulation, we have carefully examined the effect of indomethacin on the secretion of PA in granulosa and theca-interstitial (TI) cells following hCG or GnRH agonist administration in PMSG-primed hypophysectomized immature rats. We have also studies in vitro action of this compound on PA secretion in granulosa cells. The results indicate that indomethacin can only suppress hCG- and GnRH agonist-induced PA secretion, but not suppress the ovarian content of these enzymes.     

大鼠颗粒细胞tPA和PAI-1表达的激素调控

本文研究了促性腺激素(FSH和LH)和促性腺激素释放激素(GnRH)类似物(GnRHa)对大鼠颗粒细胞(GC)tPA和PAI-1表达的调节。(1)FSH和LH及GnRHa或大蓟二萜醇-12-14烷基-13乙酸盐(PMA)可单独刺激GC分泌tPA;FSH(或LH)与GnRHa(或PMA)共同作用于GC时所增加的tPA活性比两者单独作用之和要高;(2)FSH和LH降低GC的PAI-1活性,而GnRHa和PMA则明显刺激GC的PAI-1活性和PAI-1 mRNA水平;(3)GnRHa和PMA刺激GC的PAI-1活性和PAI-1的mRNA水平;但在FSH或LH存在的情况下这种刺激受到完全抑制。因此促性腺激素和GnRHa对GC tPA和PAI-1表达的调控机制可能是不同的。     

小鼠Sertoli细胞tPA和PAI-1基因表达的激素调节

本文首次提出证据表明:(1)在FSH和cAMP生成因子作用下,小鼠Sertoli细胞主要分泌tPA,而Leydig细胞主要产生uPA;(2)Sertoli细胞也具有分泌PAI-1的功能。PAI-1基因表达明显受FSH、生长因子和GnRH激发;(3)因为在各种激素作用下Sertoli细胞分泌到培液中的tPA和PAI-1活性蛋白与细胞中的tPA和PAI-1mRNA增加一致,激素是在转录水平上调节小鼠Sertoli细胞tPA和PAl-1的生物合成。Sertoli细胞产生的tPA可能与精子发生有关。