Lambert A, Talbot J A, Mitchell R, Robertson W R
Department of Medicine (Clinical Biochemistry), University of Manchester, Hope Hospital, Salford, UK.
Acta Endocrinol (Copenh). 1991 Sep;125(3):286-90. doi: 10.1530/acta.0.1250286.
We have examined the effect of inhibition of protein kinase C activity by staurosporine on estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Staurosporine lead to a dose-related increase in estradiol secretion independent of FSH, such that with 100 nmol/l staurosporine basal estradiol levels increased 10-fold. The maximal response seen with staurosporine alone (100 nmol/l) or in combination with FSH (0.4-8 IU/l) was similar to that seen with a saturating dose of FSH (8 IU/l). There was no evidence of synergy between FSH and staurosporine. Activation of protein kinase C by phorbol 12,13 dibutyrate (10(-7) mol/l) resulted in a 53-74% inhibition of estradiol production provoked by FSH (8 IU/l), staurosporine (5-100 nmol/l) or staurosporine in combination with FSH. Staurosporine (5-100 nmol/l), in the absence or presence of FSH, was unable to overcome inhibition of estradiol secretion by phorbol ester, indicating the presence of at least two independent binding sites on protein kinase C for these molecules. Forskolin (1 mumol/l)- and dibutyryl cAMP (1 mmol/l)-stimulated estradiol secretion was inhibited by 31 +/- 5% and 64 +/- 5% respectively, by phorbol 12,13 dibutyrate (10(-7) mol/l). We conclude that FSH-induced estradiol secretion in immature rat Sertoli cells is affected by protein kinase C activity.
我们研究了星形孢菌素抑制蛋白激酶C活性对从8 - 10日龄大鼠分离的支持细胞分泌雌二醇的影响。星形孢菌素导致雌二醇分泌呈剂量相关增加，且与促卵泡激素（FSH）无关，例如在100 nmol/l星形孢菌素作用下，基础雌二醇水平增加了10倍。单独使用星形孢菌素（100 nmol/l）或与FSH（0.4 - 8 IU/l）联合使用时所观察到的最大反应，与使用饱和剂量FSH（8 IU/l）时相似。没有证据表明FSH与星形孢菌素之间存在协同作用。佛波醇12,13 - 二丁酸酯（10⁻⁷ mol/l）激活蛋白激酶C导致FSH（8 IU/l）、星形孢菌素（5 - 100 nmol/l）或星形孢菌素与FSH联合诱导的雌二醇产生受到53 - 74%的抑制。在不存在或存在FSH的情况下，星形孢菌素（5 - 100 nmol/l）均无法克服佛波酯对雌二醇分泌的抑制作用，这表明蛋白激酶C上存在至少两个独立的这些分子结合位点。佛波醇12,13 - 二丁酸酯（10⁻⁷ mol/l）分别使福斯高林（1 μmol/l）和二丁酰环磷腺苷（1 mmol/l）刺激的雌二醇分泌受到31±5%和64±5%的抑制。我们得出结论，未成熟大鼠支持细胞中FSH诱导的雌二醇分泌受蛋白激酶C活性影响。
