Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells
Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells
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DOI：
10.1210/jc.2003-030704
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发表时间：
2003-10-01
影响因子：
5.8
通讯作者：
Voutilainen, R
中科院分区：
文献类型：
--
作者：
Liu, JQ;Kuulasmaa, T;Voutilainen, R
激活素和抑制素在卵巢功能的调节中常常是拮抗的。 TGFbeta III 型受体（β聚糖）已被确定为辅助受体，可增强抑制素与激活素 II 型受体的结合，从而阻止激活素与其受体的结合。在这项研究中，我们表征了正常卵巢和性索间质瘤以及体外受精女性培养的人颗粒黄体细胞中β聚糖基因的表达和调控模式。通过 RT-PCR 或 Northern blotting 检测正常卵巢颗粒细胞、卵泡膜细胞和基质细胞以及颗粒黄体细胞中 β 聚糖 mRNA 的表达。免疫组织化学分析显示，在正常卵巢的窦状和排卵前卵泡颗粒和膜细胞以及黄体中，β聚糖呈阳性染色。此外，在绝大多数颗粒细胞瘤、卵泡膜细胞瘤和纤维瘤中检测到β聚糖表达，与纤维卵泡膜瘤相比，颗粒细胞瘤中的染色较弱。在培养的颗粒黄体细胞中，FSH 和 LH 处理可剂量依赖性地增加 β-聚糖 mRNA 的积累，蛋白激酶 A 激活剂二丁酰 cAMP 和蛋白激酶 C 抑制剂星形孢菌素也是如此。相比之下，蛋白激酶C激活剂12-O-十四酰佛波醇13-乙酸酯对β聚糖mRNA水平没有显着影响。用前列腺素 E-2 及其受体 EP2 亚型激动剂布他前列素治疗可增加 β-聚糖 mRNA 积累和黄体酮分泌，呈剂量和时间依赖性。总之，β聚糖基因在正常人卵巢类固醇生成细胞和性索间质卵巢肿瘤中表达。促性腺激素和前列腺素 E2 可能通过蛋白激酶 A 途径上调其 mRNA 在培养的颗粒黄体细胞中的积累。 Betaglycan基因的特异性表达和调控模式可能与人卵巢中抑制素对激活素信号转导的功能拮抗作用有关。
Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E-2 and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E2, probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to activin signal transduction in human ovaries.