Gocze P M, Beamer W G, de Jong F H, Freeman D A
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Gynecol Oncol. 1997 Apr;65(1):143-8. doi: 10.1006/gyno.1997.4635.
Granulosa cell tumors spontaneously occur in approximately 10-25% of female (SWR x SWXJ-9) F1 mice. The present studies were designed to test whether tumor-bearing mice produce a distinct hormonal profile by which they could be identified and determine whether cultured tumor cells are responsive to hormones and growth factors that regulate normal granulosa cells. Samples of female mouse blood taken from age 3 to 10 weeks allowed estimation of serum FSH, 17beta-estradiol, and inhibin levels for normal mice and for mice destined to develop tumors. These studies indicated that FSH and 17beta-estradiol values differed between normal and tumor-bearing animals, but overlapped sufficiently that such values could not accurately predict the tumor-bearing state. Inhibin concentrations did differentiate normal from tumor-bearing animals in all cases. Increased levels of inhibin were observed coincident in time with visibly detectable tumors within the ovaries. Compared to inhibin synthesis in vivo, hormonal responsiveness in vitro was much more variable. Steroidogenesis was stimulated in all tumors by dibutyryl-cAMP and low-density lipoprotein (LDL). Some, but not all, tumors responded to IGF1, EGF, FSH, and hCG. In about one-half of the tumors tested, FSH could induce hCG or dibutyryl-cAMP responsiveness. IGF1 pretreatment consistently increased the responsiveness of tumor cells stimulated by dibutyryl-cAMP and LDL. Production of inhibin by isolated tumor cells was detectable and decreased by EGF or dibutyryl-cAMP treatments. We conclude that granulosa tumor cell secretion of inhibin may be under different control than secretion from normal granulosa cells and acts as an excellent marker for these tumors.
颗粒细胞瘤在大约10%-25%的雌性（SWR×SWXJ-9）F1小鼠中自发发生。本研究旨在测试荷瘤小鼠是否产生一种独特的激素谱，通过该激素谱可以识别它们，并确定培养的肿瘤细胞是否对调节正常颗粒细胞的激素和生长因子有反应。采集3至10周龄雌性小鼠的血液样本，用于估计正常小鼠和注定要发生肿瘤的小鼠的血清促卵泡激素（FSH）、17β-雌二醇和抑制素水平。这些研究表明，正常动物和荷瘤动物的FSH和17β-雌二醇值存在差异，但重叠程度足以使这些值无法准确预测荷瘤状态。在所有情况下，抑制素浓度确实能区分正常动物和荷瘤动物。观察到抑制素水平升高与卵巢内可见的可检测肿瘤同时出现。与体内抑制素合成相比，体外激素反应性的变化要大得多。二丁酰环磷腺苷（dibutyryl-cAMP）和低密度脂蛋白（LDL）刺激所有肿瘤的类固醇生成。一些但并非所有肿瘤对胰岛素样生长因子1（IGF1）、表皮生长因子（EGF）、FSH和人绒毛膜促性腺激素（hCG）有反应。在大约一半的测试肿瘤中，FSH可诱导hCG或二丁酰环磷腺苷反应性。IGF1预处理持续增加二丁酰环磷腺苷和LDL刺激的肿瘤细胞反应性。分离的肿瘤细胞可检测到抑制素的产生，EGF或二丁酰环磷腺苷处理可使其减少。我们得出结论，颗粒细胞瘤细胞分泌抑制素可能受与正常颗粒细胞分泌不同的控制，并且是这些肿瘤的良好标志物。
